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研究生:周文城
研究生(外文):Wen-Cheng Chou
論文名稱:DNA損害反應機制調控鹼基修復路徑之探討
論文名稱(外文):Regulation of Base Excision Repair by DNA Damage Response Pathway
指導教授:沈志陽沈志陽引用關係翁芬華
指導教授(外文):Chen-Yang ShenFen-Hwa Wong
學位類別:博士
校院名稱:國立陽明大學
系所名稱:公共衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:132
中文關鍵詞:鹼基損害DNA損害反應鹼基切除修復彗星試驗RNA干擾技術磷酸化特定點突變染色體改變
外文關鍵詞:base lessionDNA damage responsebase excision repaircomet assayRNA interferencephosphorylationsite-direct mutagenesischromatin change
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DNA損害導致遺傳訊息遭到破壞,為了保護基因體穩定性,細胞內發展出可以隨時監控損害發生,並且即時引發下游反應的訊息傳遞路徑。ATM-Chk2及ATR-Chk1分屬兩條DNA損害反應路徑的關鍵樞紐,除了各自能偵測DNA雙股斷裂以及複製異常中止的DNA損害,進一步憑藉蛋白酶活性調控細胞週期停滯並且啟動對應之DNA修復路徑。細胞內除了上述DNA結構異常,尚有一大類屬是鹼基形式的損害,目前仍未建立與DNA損害反應的關連,然而鹼基損害是導致DNA單點突變的主因,研究學者僅瞭解細胞內鹼基切除修復途徑會負責這些損害類型的排除。本研究發現那些造成鹼基烷化或氧化的藥物不只是引起ATM-Chk2路徑活化,伴隨Chk2與鹼基修復之蛋白質XRCC1的結合,發現Chk2在XRCC1第284位置的酥胺酸進行磷酸化修飾。進一步分析磷酸化的功能,若是將酥胺酸置換成天冬胺酸以模擬磷酸化,雖然不影響XRCC1與鹼基修復路徑下游修復酵素既有的結合,卻發現能促進XRCC1與上游的糖解酵素及染色質的互動,推測磷酸化反應將有助於這些修復酵素在染色質的聚集以加速鹼基修復。為了證實上述的觀點,接著將XRCC1第284位置以丙胺酸取代達到阻斷磷酸化反應後,藉由鹼基修復試驗觀察到帶有此基因型的細胞在經過藥物處理,細胞內單股DNA片段累積量增加反映修復能力受到影響,同時也發現到整體的鹼基修復效率欠佳;並且從細胞存活試驗又再印證XRCC1磷酸化修飾對於細胞在藥物耐受性這方面的貢獻。綜合前面研究的結論,ATM-Chk2參與過去未曾探討的鹼基損害形式,並且透過Chk2引發XRCC1磷酸化修飾旨在促進鹼基修復路徑的進行;而ATM-Chk2-XRCC1由上至下的分子調控機制正是DNA損害反應機制的重要環節。
The DNA damage response (DDR) plays an essential role in maintaining genomic stability. ATM-Chk2 and ATR-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication forks, are two major DDRs processing structurally complicated DNA damage. In contrast, damage repaired by base excision repair (BER) is structurally simple, but whether, and how, the DDR is involved in repairing this damage is unclear. Here, we demonstrated that ATM-Chk2 was activated in the early response to oxidative and alkylation damage, known to be repaired by BER. Furthermore, Chk2 formed a complex with XRCC1, the BER scaffold protein, and phosphorylated XRCC1 in vivo and in vitro at Thr284. A mutated XRCC1 lacking Thr284 phosphorylation was linked to increased accumulation of unrepaired BER intermediate, reduced DNA repair capacity, and higher sensitivity to alkylation damage. In addition, a phosphorylation-mimic form of XRCC1 showed increased interaction with glycosylases, but not other BER proteins. Our results are consistent with the phosphorylation of XRCC1 by ATM-Chk2 facilitating recruitment of downstream BER proteins to the initial damage recognition/excision step to promote BER.
目錄
頁碼
中文摘要………………………………………………………………I
Abstract…………………………………………………………………II
目錄……………………………………………………………………III
表目錄…………………………………………………………………VI
圖目錄………………………………………………………………VII

第一章 導論…………………………………………………………1
第一節 維持基因體穩定的重要性……………………………………1
第二節 DNA損害類型與來源………………………………………3
第三節 單一蛋白酶逕行修復………………………………………5
第四節 鹼基切除修復途徑…………………………………………6
第五節 核苷酸切除修復途徑………………………………………9
第六節 DNA錯誤配對修復途徑……………………………………11
第七節 DNA雙股斷裂修復途徑……………………………………12
第八節 DNA損害反應機制………………………………………15
第九節 ATM與Chk2相關的DDR路徑……………………………16
第十節 ATR與Chk1相關的DDR路徑……………………………18

第二章 文獻回顧……………………………………………………21

第三章 實驗材料與方法……………………………………………29
第一節 細胞株培養…………………………………………………29
第二節 引子設計與核醣核酸干擾序列………………………………29
第三節 載體建構與基因表現………………………………………30
第四節 細胞內蛋白質萃取與染色質分層分離法……………………33
第五節 免疫沈澱法與免疫墨點法分析蛋白質表現量…………………34
第六節 試管內進行蛋白質結合分析與磷酸化反應試驗………………35
第七節 免疫螢光染色法……………………………………………36
第八節 細胞週期同步化與分析……………………………………37
第九節 NAD(P)H耗盡試驗…………………………………………37
第十節 慧星試驗……………………………………………………38
第十一節 細胞存活度試驗…………………………………………39

第四章 實驗結果……………………………………………………48
第一節 鹼基損害啟動ATM-Chk2相關的DNA損害反應……………48
第二節 ATM調控鹼基損害引發的Chk2磷酸化……………………48
第三節 鹼基損害不必仰賴DNA複製即可啟動DNA損害反應………49
第四節 DNA損害反應與細胞內鹼基損害的修復過程有關…………50
第五節 Chk2參與BER,推測是透過與XRCC1的結合……………51
第六節 試管內結合試驗確認Chk2與XRCC1彼此的結合…………52
第七節 Chk2造成XRCC1T284與XRCC1T304磷酸化…………………53
第八節 鹼基損害引發Chk2對XRCC1T284磷酸化…………………56
第九節 XRCC1T284D模擬磷酸化的突變更容易與糖解酵素結合………57
第十節 糖解酵素促進磷酸化之XRCC1對受損DNA的親合力……59
第十一節 XRCC1T284A影響BER能力及增加細胞對MMS的敏感性…60

第五章 討論…………………………………………………………83
第一節 MMS活化ATM-Chk2與ATR-Chk1磷酸化傳遞路徑………83
第二節 MMS造成之鹼基損害需要不同的DNA修復機制協助復原…84
第三節 鹼基損害引發ATM-Chk2活化路徑…………………………85
第四節 XRCC1磷酸化在BER的角色……………………………88
第五節 磷酸化及其他後轉譯修飾作用對於BER功能的影響………91
第六節 DDR與DNA修復機制互為參與彼此的調控………………92
第七節 不同的BER試驗所代表的意義與可信賴度…………………94
第八節 XRCC1磷酸化調控與MMS毒性的關連性…………………95
第九節 未來研究方向……………………………………………96

第六章 參考文獻……………………………………………………99

附錄…………………………………………………………………120
Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15: 2177-2196
Adamson AW, Kim WJ, Shangary S, Baskaran R, and Brown KD (2002) ATM is activated in response to N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA alkylation. J Biol Chem 277: 38222-38229
Ahnesorg P, Smith P, and Jackson SP (2006) XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124: 301-313
Alekseyev YO, Hamm ML, and Essigmann JM (2004) Aflatoxin B1 formamidopyrimidine adducts are preferentially repaired by the nucleotide excision repair pathway in vivo. Carcinogenesis 25: 1045-1051
Ali A, Zhang J, Bao S, Liu I, Otterness D, Dean NM, Abraham RT, and Wang XF (2004) Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes Dev 18: 249-254
Almeida KH and Sobol RW (2007) A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair (Amst) 6: 695-711
Auclair Y, Rouget R, Affar eB, and Drobetsky EA (2008) ATR kinase is required for global genomic nucleotide excision repair exclusively during S phase in human cells. Proc Natl Acad Sci U S A 105: 17896-17901
Bakkenist CJ and Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506
Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, and Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281: 1674-1677
Bartek J and Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3: 421-429
Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, and Bartek J (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864-870
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, Takaoka M, Nakagawa H, Tort F, Fugger K, Johansson F, Sehested M, Andersen CL, Dyrskjot L, Orntoft T, Lukas J, Kittas C, Helleday T, Halazonetis TD, Bartek J, and Gorgoulis VG (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444: 633-637
Bekker-Jensen S, Lukas C, Melander F, Bartek J, and Lukas J (2005) Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1. J Cell Biol 170: 201-211
Beranek DT (1990) Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutat Res 231: 11-30
Berkovich E, Monnat RJ, Jr., and Kastan MB (2007) Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol 9: 683-690
Bhakat KK, Hazra TK, and Mitra S (2004) Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity. Nucleic Acids Res 32: 3033-3039
Bhakat KK, Mokkapati SK, Boldogh I, Hazra TK, and Mitra S (2006) Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. Mol Cell Biol 26: 1654-1665
Bodmer W, Bielas JH, and Beckman RA (2008) Genetic instability is not a requirement for tumor development. Cancer Res 68: 3558-3560
Bomgarden RD, Lupardus PJ, Soni DV, Yee MC, Ford JM, and Cimprich KA (2006) Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase eta on ATR checkpoint signaling. EMBO J 25: 2605-2614
Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, and Mer G (2006) Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127: 1361-1373
Branzei D and Foiani M (2007) RecQ helicases queuing with Srs2 to disrupt Rad51 filaments and suppress recombination. Genes Dev 21: 3019-3026
Brem R, Fernet M, Chapot B, and Hall J (2008) The methyl methanesulfonate induced S-phase delay in XRCC1-deficient cells requires ATM and ATR. DNA Repair (Amst) 7: 849-857
Brem R and Hall J (2005) XRCC1 is required for DNA single-strand break repair in human cells. Nucleic Acids Res 33: 2512-2520
Brott D, Gould S, Jones H, Schofield J, Prior H, Valentin JP, Bjurstrom S, Kenne K, Schuppe-Koistinen I, Katein A, Foster-Brown L, Betton G, Richardson R, Evans G, and Louden C (2005) Biomarkers of drug-induced vascular injury. Toxicol Appl Pharmacol 207: 441-445
Brown EJ and Baltimore D (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev 14: 397-402
Brown KD, Rathi A, Kamath R, Beardsley DI, Zhan Q, Mannino JL, and Baskaran R (2003) The mismatch repair system is required for S-phase checkpoint activation. Nat Genet 33: 80-84
Bugreev DV, Mazina OM, and Mazin AV (2006) Rad54 protein promotes branch migration of Holliday junctions. Nature 442: 590-593
Burrows AE and Elledge SJ (2008) How ATR turns on: TopBP1 goes on ATRIP with ATR. Genes Dev 22: 1416-1421
Buscemi G, Perego P, Carenini N, Nakanishi M, Chessa L, Chen J, Khanna K, and Delia D (2004) Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks. Oncogene 23: 7691-7700
Buscemi G, Savio C, Zannini L, Micciche F, Masnada D, Nakanishi M, Tauchi H, Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, and Delia D (2001) Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol 21: 5214-5222
Caldecott KW (2003) XRCC1 and DNA strand break repair. DNA Repair (Amst) 2: 955-969
Caldecott KW (2008) Single-strand break repair and genetic disease. Nat Rev Genet 9: 619-631
Campalans A, Marsin S, Nakabeppu Y, O'connor TR, Boiteux S, and Radicella JP (2005) XRCC1 interactions with multiple DNA glycosylases: a model for its recruitment to base excision repair. DNA Repair (Amst) 4: 826-835
Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, and Siliciano JD (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281: 1677-1679
Caporali S, Falcinelli S, Starace G, Russo MT, Bonmassar E, Jiricny J, and D'Atri S (2004) DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol Pharmacol 66: 478-491
Chaturvedi P, Eng WK, Zhu Y, Mattern MR, Mishra R, Hurle MR, Zhang X, Annan RS, Lu Q, Faucette LF, Scott GF, Li X, Carr SA, Johnson RK, Winkler JD, and Zhou BB (1999) Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Oncogene 18: 4047-4054
Cimprich KA and Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9: 616-627
Cleaver JE (2005) Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat Rev Cancer 5: 564-573
Cline SD and Hanawalt PC (2003) Who's on first in the cellular response to DNA damage? Nat Rev Mol Cell Biol 4: 361-372
Cortez D, Glick G, and Elledge SJ (2004) Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Natl Acad Sci U S A 101: 10078-10083
Cortez D, Guntuku S, Qin J, and Elledge SJ (2001) ATR and ATRIP: partners in checkpoint signaling. Science 294: 1713-1716
Costanzo V, Shechter D, Lupardus PJ, Cimprich KA, Gottesman M, and Gautier J (2003) An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol Cell 11: 203-213
Cybulski C, Gorski B, Debniak T, Gliniewicz B, Mierzejewski M, Masojc B, Jakubowska A, Matyjasik J, Zlowocka E, Sikorski A, Narod SA, and Lubinski J (2004) NBS1 is a prostate cancer susceptibility gene. Cancer Res 64: 1215-1219
David SS, O'Shea VL, and Kundu S (2007) Base-excision repair of oxidative DNA damage. Nature 447: 941-950
De BR and van LN (2004) Endogenous DNA damage in humans: a review of quantitative data. Mutagenesis 19: 169-185
de LT (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 19: 2100-2110
Delacroix S, Wagner JM, Kobayashi M, Yamamoto K, and Karnitz LM (2007) The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev 21: 1472-1477
Di MR, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre' M, Nuciforo PG, Bensimon A, Maestro R, Pelicci PG, and dda di FF (2006) Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444: 638-642
Dianova II, Sleeth KM, Allinson SL, Parsons JL, Breslin C, Caldecott KW, and Dianov GL (2004) XRCC1-DNA polymerase beta interaction is required for efficient base excision repair. Nucleic Acids Res 32: 2550-2555
Dong Z and Tomkinson AE (2006) ATM mediates oxidative stress-induced dephosphorylation of DNA ligase IIIalpha. Nucleic Acids Res 34: 5721-279
Downs JA, Nussenzweig MC, and Nussenzweig A (2007) Chromatin dynamics and the preservation of genetic information. Nature 447: 951-958
El-Shemerly M, Hess D, Pyakurel AK, Moselhy S, and Ferrari S (2008) ATR-dependent pathways control hEXO1 stability in response to stalled forks. Nucleic Acids Res 36: 511-519
Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, and Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343: 1350-1354
Fan J, Otterlei M, Wong HK, Tomkinson AE, and Wilson DM, III (2004) XRCC1 co-localizes and physically interacts with PCNA. Nucleic Acids Res 32: 2193-2201
Fanning E, Klimovich V, and Nager AR (2006) A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res 34: 4126-4137
Fernandez-Capetillo O and Nussenzweig A (2008) ATM breaks into heterochromatin. Mol Cell 31: 303-304
Fortini P and Dogliotti E (2007) Base damage and single-strand break repair: mechanisms and functional significance of short- and long-patch repair subpathways. DNA Repair (Amst) 6: 398-409
Friedberg EC (2001) How nucleotide excision repair protects against cancer. Nat Rev Cancer 1: 22-33
Friedberg EC (2008) A brief history of the DNA repair field. Cell Res 18: 3-7
Friedberg EC and Meira LB (2006) Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage Version 7. DNA Repair (Amst) 5: 189-209
Gatei M, Sloper K, Sorensen C, Syljuasen R, Falck J, Hobson K, Savage K, Lukas J, Zhou BB, Bartek J, and Khanna KK (2003) Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem 278: 14806-14811
Glover JN, Williams RS, and Lee MS (2004) Interactions between BRCT repeats and phosphoproteins: tangled up in two. Trends Biochem Sci 29: 579-585
Gocke CB, Yu H, and Kang J (2005) Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates. J Biol Chem 280: 5004-5012
Goodarzi AA, Jonnalagadda JC, Douglas P, Young D, Ye R, Moorhead GB, Lees-Miller SP, and Khanna KK (2004) Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J 23: 4451-4461
Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Lobrich M, and Jeggo PA (2008) ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol Cell 31: 167-177
Goodarzi AA, Yu Y, Riballo E, Douglas P, Walker SA, Ye R, Harer C, Marchetti C, Morrice N, Jeggo PA, and Lees-Miller SP (2006) DNA-PK autophosphorylation facilitates Artemis endonuclease activity. EMBO J 25: 3880-3889
Goode EL, Ulrich CM, and Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11: 1513-1530
Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA, Jr., Kastrinakis NG, Levy B, Kletsas D, Yoneta A, Herlyn M, Kittas C, and Halazonetis TD (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434: 907-913
Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT, Lucchesi JC, Khanna KK, Ludwig T, and Pandita TK (2005) Involvement of human MOF in ATM function. Mol Cell Biol 25: 5292-5305
Hagen L, Kavli B, Sousa MM, Torseth K, Liabakk NB, Sundheim O, Pena-Diaz J, Otterlei M, Horning O, Jensen ON, Krokan HE, and Slupphaug G (2008) Cell cycle-specific UNG2 phosphorylations regulate protein turnover, activity and association with RPA. EMBO J 27: 51-61
Haince JF, Kozlov S, Dawson VL, Dawson TM, Hendzel MJ, Lavin MF, and Poirier GG (2007) Ataxia telangiectasia mutated (ATM) signaling network is modulated by a novel poly(ADP-ribose)-dependent pathway in the early response to DNA-damaging agents. J Biol Chem 282: 16441-16453
Haince JF, McDonald D, Rodrigue A, Dery U, Masson JY, Hendzel MJ, and Poirier GG (2008) PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem 283: 1197-1208
Halazonetis TD, Gorgoulis VG, and Bartek J (2008) An oncogene-induced DNA damage model for cancer development. Science 319: 1352-1355
Hanahan D and Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57-70
Hanawalt PC and Spivak G (2008) Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 9: 958-970
Hasan S, El-Andaloussi N, Hardeland U, Hassa PO, Burki C, Imhof R, Schar P, and Hottiger MO (2002) Acetylation regulates the DNA end-trimming activity of DNA polymerase beta. Mol Cell 10: 1213-1222
Hegde ML, Hazra TK, and Mitra S (2008) Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells. Cell Res 18: 27-47
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de TN, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, and Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352: 997-1003
Helt CE, Cliby WA, Keng PC, Bambara RA, and O'Reilly MA (2005) Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage. J Biol Chem 280: 1186-1192
hm-Daphi J, Sass C, and Alberti W (2000) Comparison of biological effects of DNA damage induced by ionizing radiation and hydrogen peroxide in CHO cells. Int J Radiat Biol 76: 67-75
Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411: 366-374
Hollis T, Ichikawa Y, and Ellenberger T (2000) DNA bending and a flip-out mechanism for base excision by the helix-hairpin-helix DNA glycosylase, Escherichia coli AlkA. EMBO J 19: 758-766
Horton JK, Stefanick DF, Kedar PS, and Wilson SH (2007a) ATR signaling mediates an S-phase checkpoint after inhibition of poly(ADP-ribose) polymerase activity. DNA Repair (Amst) 6: 742-750
Horton JK, Stefanick DF, Naron JM, Kedar PS, and Wilson SH (2005) Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest after DNA methylating agent exposure. J Biol Chem 280: 15773-15785
Horton JK, Watson M, Stefanick DF, Shaughnessy DT, Taylor JA, and Wilson SH (2008) XRCC1 and DNA polymerase beta in cellular protection against cytotoxic DNA single-strand breaks. Cell Res 18: 48-63
Horton JK and Wilson SH (2007b) Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency. DNA Repair (Amst) 6: 530-543
Hu J, Imam SZ, Hashiguchi K, de Souza-Pinto NC, and Bohr VA (2005) Phosphorylation of human oxoguanine DNA glycosylase (alpha-OGG1) modulates its function. Nucleic Acids Res 33: 3271-3282
Hussain SP, Hofseth LJ, and Harris CC (2003) Radical causes of cancer. Nat Rev Cancer 3: 276-285
Huyen Y, Zgheib O, Ditullio RA, Jr., Gorgoulis VG, Zacharatos P, Petty TJ, Sheston EA, Mellert HS, Stavridi ES, and Halazonetis TD (2004) Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432: 406-411
Ismail IH, Nystrom S, Nygren J, and Hammarsten O (2005) Activation of ataxia telangiectasia mutated by DNA strand break-inducing agents correlates closely with the number of DNA double strand breaks. J Biol Chem 280: 4649-4655
Jazayeri A, Balestrini A, Garner E, Haber JE, and Costanzo V (2008) Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J 27: 1953-1962
Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, and Jackson SP (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8: 37-45
Jeggo P and Lobrich M (2006) Radiation-induced DNA damage responses. Radiat Prot Dosimetry 122: 124-127
Jiricny J (2006) The multifaceted mismatch-repair system. Nat Rev Mol Cell Biol 7: 335-346
Kaina B, Christmann M, Naumann S, and Roos WP (2007) MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents. DNA Repair (Amst) 6: 1079-1099
Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, and Yasui A (2007) A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J 26: 2094-2103
Kartalou M and Essigmann JM (2001a) Recognition of cisplatin adducts by cellular proteins. Mutat Res 478: 1-21
Kartalou M and Essigmann JM (2001b) Mechanisms of resistance to cisplatin. Mutat Res 478: 23-43
Kastan MB and Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432: 316-323
Kedar PS, Stefanick DF, Horton JK, and Wilson SH (2008) Interaction between PARP-1 and ATR in mouse fibroblasts is blocked by PARP inhibition. DNA Repair (Amst) 7: 1787-1798
Khanna KK, Keating KE, Kozlov S, Scott S, Gatei M, Hobson K, Taya Y, Gabrielli B, Chan D, Lees-Miller SP, and Lavin MF (1998) ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet 20: 398-400
Kim H, Chen J, and Yu X (2007a) Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. Science 316: 1202-1205
Kim MA, Kim HJ, Brown AL, Lee MY, Bae YS, Park JI, Kwak JY, Chung JH, and Yun J (2007b) Identification of novel substrates for human checkpoint kinase Chk1 and Chk2 through genome-wide screening using a consensus Chk phosphorylation motif. Exp Mol Med 39: 205-212
Kim YC, Gerlitz G, Furusawa T, Catez F, Nussenzweig A, Oh KS, Kraemer KH, Shiloh Y, and Bustin M (2009) Activation of ATM depends on chromatin interactions occurring before induction of DNA damage. Nat Cell Biol 11: 92-96
Kitagawa R, Bakkenist CJ, McKinnon PJ, and Kastan MB (2004) Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 18: 1423-1438
Kruse JP and Gu W (2008) SnapShot: p53 posttranslational modifications. Cell 133: 930
Kumagai A, Lee J, Yoo HY, and Dunphy WG (2006) TopBP1 activates the ATR-ATRIP complex. Cell 124: 943-955
Kurz EU and Lees-Miller SP (2004) DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst) 3: 889-900
Lavin MF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9: 759-769
Lee J, Kumagai A, and Dunphy WG (2007) The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J Biol Chem 282: 28036-28044
Lee JH and Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304: 93-96
Lee JH and Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308: 551-554
Lee JS, Collins KM, Brown AL, Lee CH, and Chung JH (2000) hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404: 201-204
Li X and Heyer WD (2008) Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18: 99-113
Likhite VS, Cass EI, Anderson SD, Yates JR, and Nardulli AM (2004) Interaction of estrogen receptor alpha with 3-methyladenine DNA glycosylase modulates transcription and DNA repair. J Biol Chem 279: 16875-16882
Lin WC, Lin FT, and Nevins JR (2001) Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev 15: 1833-1844
Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362: 709-715
Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jorgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, Metalnikov P, Nguyen V, Pasculescu A, Jin J, Park JG, Samson LD, Woodgett JR, Russell RB, Bork P, Yaffe MB, and Pawson T (2007) Systematic discovery of in vivo phosphorylation networks. Cell 129: 1415-1426
Liu Y, Tarsounas M, O'regan P, and West SC (2007) Role of RAD51C and XRCC3 in genetic recombination and DNA repair. J Biol Chem 282: 1973-1979
Loeb LA (1991) Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 51: 3075-3079
Loeb LA, Bielas JH, and Beckman RA (2008) Cancers exhibit a mutator phenotype: clinical implications. Cancer Res 68: 3551-3557
Loeb LA and Monnat RJ, Jr. (2008) DNA polymerases and human disease. Nat Rev Genet 9: 594-604
Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J, Sarno S, Meggio F, Pinna LA, and Caldecott KW (2004) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell 117: 17-28
Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van DJ, Nussenzweig A, Paull TT, Alt FW, and Chen J (2006) MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 21: 187-200
Lu X, Bocangel D, Nannenga B, Yamaguchi H, Appella E, and Donehower LA (2004) The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Mol Cell 15: 621-634
Lundin C, North M, Erixon K, Walters K, Jenssen D, Goldman AS, and Helleday T (2005) Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks. Nucleic Acids Res 33: 3799-3811
Luo H, Chan DW, Yang T, Rodriguez M, Chen BP, Leng M, Mu JJ, Chen D, Songyang Z, Wang Y, and Qin J (2004) A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment. Mol Cell Biol 24: 8356-8365
Mallette FA, Gaumont-Leclerc MF, and Ferbeyre G (2007) The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev 21: 43-48
Manke IA, Lowery DM, Nguyen A, and Yaffe MB (2003) BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302: 636-639
Mao Z, Bozzella M, Seluanov A, and Gorbunova V (2008) DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells. Cell Cycle 7: 2902-2906
Marini F, Nardo T, Giannattasio M, Minuzzo M, Stefanini M, Plevani P, and Muzi FM (2006) DNA nucleotide excision repair-dependent signaling to checkpoint activation. Proc Natl Acad Sci U S A 103: 17325-17330
Marsin S, Vidal AE, Sossou M, Menissier-de MJ, Le PF, Boiteux S, de MG, and Radicella JP (2003) Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1. J Biol Chem 278: 44068-44074
Massague J (2004) G1 cell-cycle control and cancer. Nature 432: 298-306
Masson M, Niedergang C, Schreiber V, Muller S, Menissier-de MJ, and de MG (1998) XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol 18: 3563-3571
Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER, III, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, and Elledge SJ (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316: 1160-1166
Mazina OM and Mazin AV (2008) Human Rad54 protein stimulates human Mus81-Eme1 endonuclease. Proc Natl Acad Sci U S A 105: 18249-18254
McCulloch SD and Kunkel TA (2008) The fidelity of DNA synthesis by eukaryotic replicative and translesion synthesis polymerases. Cell Res 18: 148-161
Meijers-Heijboer H, van den OA, Klijn J, Wasielewski M, de SA, Oldenburg R, Hollestelle A, Houben M, Crepin E, van Veghel-Plandsoen M, Elstrodt F, van DC, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton D, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Evans DG, Houlston R, Murday V, Narod S, Peretz T, Peto J, Phelan C, Zhang HX, Szabo C, Devilee P, Goldgar D, Futreal PA, Nathanson KL, Weber B, Rahman N, and Stratton MR (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31: 55-59
Metz AH, Hollis T, and Eichman BF (2007) DNA damage recognition and repair by 3-methyladenine DNA glycosylase I (TAG). EMBO J 26: 2411-2420
Mochan TA, Venere M, DiTullio RA, Jr., and Halazonetis TD (2003) 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res 63: 8586-8591
Mordes DA, Glick GG, Zhao R, and Cortez D (2008) TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev 22: 1478-1489
Morrison C, Sonoda E, Takao N, Shinohara A, Yamamoto K, and Takeda S (2000) The controlling role of ATM in homologous recombinational repair of DNA damage. EMBO J 19: 463-471
Muller-Weeks S, Mastran B, and Caradonna S (1998) The nuclear isoform of the highly conserved human uracil-DNA glycosylase is an Mr 36,000 phosphoprotein. J Biol Chem 273: 21909-21917
Nakamura J, Asakura S, Hester SD, de MG, Caldecott KW, and Swenberg JA (2003) Quantitation of intracellular NAD(P)H can monitor an imbalance of DNA single strand break repair in base excision repair deficient cells in real time. Nucleic Acids Res 31: e104
Nakamura K, Sakai W, Kawamoto T, Bree RT, Lowndes NF, Takeda S, and Taniguchi Y (2006) Genetic dissection of vertebrate 53BP1: a major role in non-homologous end joining of DNA double strand breaks. DNA Repair (Amst) 5: 741-749
Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25: 5832-5836
Nazarkina ZK, Khodyreva SN, Marsin S, Lavrik OI, and Radicella JP (2007) XRCC1 interactions with base excision repair DNA intermediates. DNA Repair (Amst) 6: 254-264
Nelson HH, Kelsey KT, Mott LA, and Karagas MR (2002) The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction. Cancer Res 62: 152-155
Nghiem P, Park PK, Kim Y, Vaziri C, and Schreiber SL (2001) ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation. Proc Natl Acad Sci U S A 98: 9092-9097
Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, and Hanaoka F (2005) Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma pigmentosum group C protein. Mol Cell Biol 25: 5664-5674
O'Neill T, Giarratani L, Chen P, Iyer L, Lee CH, Bobiak M, Kanai F, Zhou BB, Chung JH, and Rathbun GA (2002) Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach. J Biol Chem 277: 16102-16115
Olive PL and Banath JP (2006) The comet assay: a method to measure DNA damage in individual cells. Nat Protoc 1: 23-29
Ostling O and Johanson KJ (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 123: 291-298
Pachkowski BF, Winkel S, Kubota Y, Swenberg JA, Millikan RC, and Nakamura J (2006) XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. Cancer Res 66: 2860-2868
Parsons JL, Tait PS, Finch D, Dianova II, Allinson SL, and Dianov GL (2008) CHIP-Mediated Degradation and DNA Damage-Dependent Stabilization Regulate Base Excision Repair Proteins. Mol Cell 29: 477-487
Paull TT and Gellert M (2000) A mechanistic basis for Mre11-directed DNA joining at microhomologies. Proc Natl Acad Sci U S A 97: 6409-6414
Petermann E, Keil C, and Oei SL (2006) Roles of DNA ligase III and XRCC1 in regulating the switch between short patch and long patch BER. DNA Repair (Amst) 5: 544-555
Peterson CL and Cote J (2004) Cellular machineries for chromosomal DNA repair. Genes Dev 18: 602-616
Prasad R, Liu Y, Deterding LJ, Poltoratsky VP, Kedar PS, Horton JK, Kanno S, Asagoshi K, Hou EW, Khodyreva SN, Lavrik OI, Tomer KB, Yasui A, and Wilson SH (2007) HMGB1 is a cofactor in mammalian base excision repair. Mol Cell 27: 829-841
Rajagopalan H and Lengauer C (2004) Aneuploidy and cancer. Nature 432: 338-341
Raschle M, Knipsheer P, Enoiu M, Angelov T, Sun J, Griffith JD, Ellenberger TE, Scharer OD, and Walter JC (2008) Mechanism of replication-coupled DNA interstrand crosslink repair. Cell 134: 969-980
Riha K, Heacock ML, and Shippen DE (2006) The role of the nonhomologous end-joining DNA double-strand break repair pathway in telomere biology. Annu Rev Genet 40: 237-277
Rinne ML, He Y, Pachkowski BF, Nakamura J, and Kelley MR (2005) N-methylpurine DNA glycosylase overexpression increases alkylation sensitivity by rapidly removing non-toxic 7-methylguanine adducts. Nucleic Acids Res 33: 2859-2867
Rothkamm K, Kruger I, Thompson LH, and Lobrich M (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23: 5706-5715
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, and Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73: 39-85
Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, and Kouzarides T (2004) Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119: 603-614
Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, and Jackson SP (2007) Human CtIP promotes DNA end resection. Nature 450: 509-514
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, and Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268: 1749-1753
Sedgwick B (2004) Repairing DNA-methylation damage. Nat Rev Mol Cell Biol 5: 148-157
Seo GJ, Kim SE, Lee YM, Lee JW, Lee JR, Hahn MJ, and Kim ST (2003) Determination of substrate specificity and putative substrates of Chk2 kinase. Biochem Biophys Res Commun 304: 339-343
Shiloh Y (2003) ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3: 155-168
Shreeram S, Demidov ON, Hee WK, Yamaguchi H, Onishi N, Kek C, Timofeev ON, Dudgeon C, Fornace AJ, Anderson CW, Minami Y, Appella E, and Bulavin DV (2006) Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell 23: 757-764
Shrivastav M, De Haro LP, and Nickoloff JA (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18: 134-147
Shuck SC, Short EA, and Turchi JJ (2008) Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology. Cell Res 18: 64-72
Slupphaug G, Kavli B, and Krokan HE (2003) The interacting pathways for prevention and repair of oxidative DNA damage. Mutat Res 531: 231-251
Sobhian B, Shao G, Lilli DR, Culhane AC, Moreau LA, Xia B, Livingston DM, and Greenberg RA (2007) RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316: 1198-1202
Sorensen CS, Hansen LT, Dziegielewski J, Syljuasen RG, Lundin C, Bartek J, and Helleday T (2005) The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 7: 195-201
Soutoglou E (2008) DNA lesions and DNA damage response: even long lasting relationships need a "break". Cell Cycle 7: 3653-3658
Soutoglou E and Misteli T (2008) Activation of the cellular DNA damage response in the absence of DNA lesions. Science 320: 1507-1510
Stiff T, Walker SA, Cerosaletti K, Goodarzi AA, Petermann E, Concannon P, O'Driscoll M, and Jeggo PA (2006) ATR-dependent phosphorylation and activation of ATM in response to UV treatment or replication fork stalling. EMBO J 25: 5775-5782
Stojic L, Mojas N, Cejka P, Di PM, Ferrari S, Marra G, and Jiricny J (2004) Mismatch repair-dependent G2 checkpoint induced by low doses of SN1 type methylating agents requires the ATR kinase. Genes Dev 18: 1331-1344
Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, and Jackson SP (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123: 1213-1226
Su TT (2006) Cellular responses to DNA damage: one signal, multiple choices. Annu Rev Genet 40: 187-208
Sun Y, Jiang X, Chen S, Fernandes N, and Price BD (2005) A role for the Tip60 histone acetyltransferase in the acetylation and activation of ATM. Proc Natl Acad Sci U S A 102: 13182-13187
Sun Y, Xu Y, Roy K, and Price BD (2007) DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol Cell Biol 27: 8502-8509
Svejstrup JQ (2002) Mechanisms of transcription-coupled DNA repair. Nat Rev Mol Cell Biol 3: 21-29
Sweasy JB, Lang T, and DiMaio D (2006) Is base excision repair a tumor suppressor mechanism? Cell Cycle 5: 250-259
Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A, and Akhtar A (2005) hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells. Mol Cell Biol 25: 6798-6810
Takanami T, Nakamura J, Kubota Y, and Horiuchi S (2005) The Arg280His polymorphism in X-ray repair cross-complementing gene 1 impairs DNA repair ability. Mutat Res 582: 135-145
Takata M, Sasaki MS, Tachiiri S, Fukushima T, Sonoda E, Schild D, Thompson LH, and Takeda S (2001) Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 21: 2858-2866
Tan Y, Raychaudhuri P, and Costa RH (2007) Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes. Mol Cell Biol 27: 1007-1016
Taylor ER and McGowan CH (2008) Cleavage mechanism of human Mus81-Eme1 acting on Holliday-junction structures. Proc Natl Acad Sci U S A 105: 3757-3762
Thompson D, Duedal S, Kirner J, McGuffog L, Last J, Reiman A, Byrd P, Taylor M, and Easton DF (2005) Cancer risks and mortality in heterozygous ATM mutation carriers. J Natl Cancer Inst 97: 813-822
Thompson LH and West MG (2000) XRCC1 keeps DNA from getting stranded. Mutat Res 459: 1-18
Thorslund T and West SC (2007) BRCA2: a universal recombinase regulator. Oncogene 26: 7720-7730
Tini M, Benecke A, Um SJ, Torchia J, Evans RM, and Chambon P (2002) Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription. Mol Cell 9: 265-277
Trenz K, Smith E, Smith S, and Costanzo V (2006) ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. EMBO J 25: 1764-1774
Tubbs JL, Pegg AE, and Tainer JA (2007) DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA alkyltransferase and its implications for cancer chemotherapy. DNA Repair (Amst) 6: 1100-1115
Venkatesan RN, Bielas JH, and Loeb LA (2006) Generation of mutator mutants during carcinogenesis. DNA Repair (Amst) 5: 294-302
Vidal AE, Boiteux S, Hickson ID, and Radicella JP (2001) XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J 20: 6530-6539
Wallace SS (2002) Biological consequences of free radical-damaged DNA bases. Free Radic Biol Med 33: 1-14
Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi SP, and Elledge SJ (2007) Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316: 1194-1198
Wang HC, Chou WC, Shieh SY, and Shen CY (2006) Ataxia telangiectasia mutated and checkpoint kinase 2 regulate BRCA1 to promote the fidelity of DNA end-joining. Cancer Res 66: 1391-1400
Wang JY and Edelmann W (2006) Mismatch repair proteins as sensors of alkylation DNA damage. Cancer Cell 9: 417-418
Wang W (2007) Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 8: 735-748
Wang Y and Qin J (2003) MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Proc Natl Acad Sci U S A 100: 15387-15392
Wei JH, Chou YF, Ou YH, Yeh YH, Tyan SW, Sun TP, Shen CY, and Shieh SY (2005) TTK/hMps1 participates in the regulation of DNA damage checkpoint response by phosphorylating CHK2 on threonine 68. J Biol Chem 280: 7748-7757
Weterings E and Chen DJ (2008) The endless tale of non-homologous end-joining. Cell Res 18: 114-124
Wiederhold L, Leppard JB, Kedar P, Karimi-Busheri F, Rasouli-Nia A, Weinfeld M, Tomkinson AE, Izumi T, Prasad R, Wilson SH, Mitra S, and Hazra TK (2004) AP endonuclease-independent DNA base excision repair in human cells. Mol Cell 15: 209-220
Wilson DM, III and Bohr VA (2007) The mechanics of base excision repair, and its relationship to aging and disease. DNA Repair (Amst) 6: 544-559
Wu L and Hickson ID (2006a) DNA helicases required for homologous recombination and repair of damaged replication forks. Annu Rev Genet 40: 279-306
Wu X, Roth JA, Zhao H, Luo S, Zheng YL, Chiang S, and Spitz MR (2005) Cell cycle checkpoints, DNA damage/repair, and lung cancer risk. Cancer Res 65: 349-357
Wu X, Shell SM, Liu Y, and Zou Y (2007) ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene 26: 757-764
Wu X, Shell SM, Yang Z, and Zou Y (2006b) Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation. Cancer Res 66: 2997-3005
Xie A, Hartlerode A, Stucki M, Odate S, Puget N, Kwok A, Nagaraju G, Yan C, Alt FW, Chen J, Jackson SP, and Scully R (2007) Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. Mol Cell 28: 1045-1057
Yacoub A, Kelley MR, and Deutsch WA (1997) The DNA repair activity of human redox/repair protein APE/Ref-1 is inactivated by phosphorylation. Cancer Res 57: 5457-5459
Yano K, Morotomi-Yano K, Wang SY, Uematsu N, Lee KJ, Asaithamby A, Weterings E, and Chen DJ (2008) Ku recruits XLF to DNA double-strand breaks. EMBO Rep 9: 91-96
Yazdi PT, Wang Y, Zhao S, Patel N, Lee EY, and Qin J (2002) SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint. Genes Dev 16: 571-582
Yoo HY, Kumagai A, Shevchenko A, Shevchenko A, and Dunphy WG (2007) Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through phosphorylation of TopBP1 by ATM. J Biol Chem 282: 17501-17506
Yoshioka K, Yoshioka Y, and Hsieh P (2006) ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell 22: 501-510
You Z, Bailis JM, Johnson SA, Dilworth SM, and Hunter T (2007) Rapid activation of ATM on DNA flanking double-strand breaks. Nat Cell Biol 9: 1311-1318
Yu X, Chini CC, He M, Mer G, and Chen J (2003) The BRCT domain is a phospho-protein binding domain. Science 302: 639-642
Zhang J, Ma Z, Treszezamsky A, and Powell SN (2005a) MDC1 interacts with Rad51 and facilitates homologous recombination. Nat Struct Mol Biol 12: 902-909
Zhang J, Willers H, Feng Z, Ghosh JC, Kim S, Weaver DT, Chung JH, Powell SN, and Xia F (2004) Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repair. Mol Cell Biol 24: 708-718
Zhang X, Miao X, Liang G, Hao B, Wang Y, Tan W, Li Y, Guo Y, He F, Wei Q, and Lin D (2005b) Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 65: 722-726
Zhuang J, Zhang J, Willers H, Wang H, Chung JH, van G, Hallahan DE, Powell SN, and Xia F (2006) Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of nonhomologous end-joining. Cancer Res 66: 1401-1408
Ziv Y, Bielopolski D, Galanty Y, Lukas C, Taya Y, Schultz DC, Lukas J, Bekker-Jensen S, Bartek J, and Shiloh Y (2006) Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat Cell Biol 8: 870-876
Zou L and Elledge SJ (2003a) Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300: 1542-1548
Zou L, Liu D, and Elledge SJ (2003b) Replication protein A-mediated recruitment and activation of Rad17 complexes. Proc Natl Acad Sci U S A 100: 13827-13832
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