(3.238.130.97) 您好!臺灣時間:2021/05/13 22:26
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:簡莛
研究生(外文):Ting
論文名稱:白色念珠菌DBF4 gene扮演菌絲負調控者的角色並具有兩條異質性且可被URA3-blaster誘導複製的對偶基因
論文名稱(外文):Candida albicans DBF4 gene with two heterologous alleles is involved in hyphae-suppression and is inducibly duplicated by URA3-blaster
指導教授:謝家慶
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生物醫學科學學系碩士班
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:185
相關次數:
  • 被引用被引用:0
  • 點閱點閱:143
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
白色念珠菌 (Candida albicans)是一種伺機性的真菌病原體,正常存在於人類口腔、消化道以及泌尿生殖道的黏膜表皮上。當免疫系統不足或發生缺陷時,白色念珠菌有能力去造成一些宿主的損傷以及疾病,例如念珠菌症 (candidiasis)和念珠菌菌血症 (candidaemia)。由於白色念珠菌為雙倍體的真核生物,且缺乏完整的有性生殖週期,加上其獨特的密碼子使用,CUG密碼子會去編碼成serine而非leucine,因此增加一些分子遺傳試驗上分析的困難度。白色念珠菌另一個顯著的生物特性是能夠轉變成三種不同的生長形態,主要分為酵母菌、真性菌絲和假性菌絲生長形態;且形態”轉換”的能力對於其致病力是非常重要的,每種不同的形態利用不同的方式與宿主互相影響,目的皆
是希望能與宿主共生或是在宿主體內散播成為伺機性的病原體。
DNA複製的機制在物種之間都是高度保留的。在真核生物中,起始 (initiation)為最重要的一個控制步驟。Dbf4-dependent kinase (DDK)由催化次單元Cdc7和調節次單元Dbf4所構成,對於真核生物DNA複製起始扮演著非常重要的角色。近年來,除了促進複製起始的功能之外,也發現了DDK扮演著和DNA損壞的檢查點控制
(DNA-damage checkpoint control)相關的角色。

在白色念珠菌中Dbf4存在三個在大部分真核生物Dbf4都高度保留的motif,從N端到C端分別命名為Dbf4-motif-N、Dbf4-motif-M和Dbf4-motif-C。在許多物種的研究發現中motif-M和motif-C和激酶的活化以及有絲分裂的功能有關,且Dbf4會利用motif-M及motif-C結合於Cdc7達到活化激酶的目的;而motif-N跟BRCT motif (BRCA C-terminal region)相似,但對於激酶的活化以及有絲分裂的功能則不是必須的,但motif-N對於DNA修復以及DNA複製的檢查則有著一定程度的影響。且由胺基酸序列的相似性預期白色念珠菌Dbf4具有和其他真核生物一樣促使DNA複製起始的功能,且為一必
要基因。
然而,令人意外的是在實驗室先前的研究發現當白色念珠菌的Cdc7在細胞內耗盡時,白色念珠菌會由原本的酵母菌生長形態轉變為菌絲生長形態,因此可以初步判定白色念珠菌的CDC7扮演著菌絲形成的負調控者角色。假設白色念珠菌的DDK功能也是屬於高度保留,白色念珠菌的Dbf4功能也是活化Cdc7,那麼白色念珠菌中的DBF4可能也是扮演著菌絲形成的負調控者角色。因此我將白色念珠菌DBF4置於可調控式的啟動子下游,藉由關閉啟動子將白色念珠菌中的Dbf4耗盡,結果發現形態出現和Cdc7耗盡時一樣的轉變,且當Dbf4耗盡,同時藉由ACT1啟動子讓白色念珠菌持續表現外源性的DBF4,結果發現因Dbf4耗盡所造成的菌絲形態回復成酵母菌形態,顯示白色念珠菌DBF4確實扮演著菌絲形成的負調控者角色,另外 Dbf4耗盡並不會影響其生長,因此由此推測白色念珠菌DBF4很可能為非必要基因;但是利用條件式剔除DBF4,卻未能得到homozygous null的突變株,顯示DBF4對於白色念珠菌還是具有某種程度的必要性。此外當Dbf4耗盡時,同時藉由ACT1啟動子讓白色念珠菌持續表現外源性的CDC7,並沒有辦法將Dbf4耗盡所造成的菌絲形態回復成酵母菌形態,加上實驗室利用yeast two-hybrid的方式確認白色念珠菌Cdc7和Dbf4有著強烈的交互作用,因此顯示白色念珠菌DBF4應該還是扮演著活化CDC7激酶的角色。另外,在建構能夠使白色念珠菌Dbf4耗盡之品系的過程中,發現兩個DBF4對偶基因具有異質性,而此種對偶基因的異質性,並非唯一存在於白色念珠菌的基因組中;同時也意外發現利用URA3-blaster剔除DBF4會
導致其中一個對偶基因orf19.5166複製,使白色念珠菌具有兩個DBF4對偶基因orf19.5166,但是在實驗室研究的其他白色念珠菌基因卻沒有發現類似的現象,因此認為此對偶基因的異質性屬於白色念珠菌DBF4的特異性。


Candida albicans is an opportunistic fungal pathogen that causes both superficial and systemic infections in immunocompromised patients. Study of C. albicans has been hampered because it is a natural diploid without complete sexual cycle and possesses an unconventional codon usage. Candida albicans is a polymorphic fungus with three major growth forms, termed yeast, pseudohyphae and hyphae. The ability to change morphology from the yeast form to a filamentous form is thought to be important for the pathogenicity of C. albicans. We have been interested in studying C. albicans genes involved in the G1-S transition of the cell cycle for their being important in morphogenesis that is associated with pathogenicity. Among those, genes encoding C. albicans equivalence of Cdc7-Dbf4 kinase complex (the Dbf4-dependent kinase, DDK), originally identified in Saccharomyces cerevisiae, are evolutionarily conserved and regulate the initiation and progression of DNA replication at least partly through phosphorylation of minichromosomal maintenance (MCM) proteins in all eukaryotes being studied. In recent studies, the DDK is thought to be an essential target inactivated by the S-phase checkpoint machinery that inhibits DNA replication. Structurally, Dbf4 protein of C. albicans is highly homologous to that of S. cerevisiae. Three small stretches of protein motifs, named Dbf4-motif-N, Dbf4-motif-M and Dbf4-motif-C, are present in all the known Dbf4 molecules from various eukaryotes. Dbf4-motif -N shows some similarity to the domain I of BRCT, which has been shown to be present in wide varieties of repair and DNA damage/replication checkpoint protein. Dbf4-motif-M and Dbf4-motif-C are shown to be sufficient for interaction and activation with catalytic subunit.
Previously, we have found that depletion of C. albicans CDC7 leads to cells with filaments. To establish the function relationship between C. albicans CDC7 (CaCDC7) and DBF4 (CaDBF4), we made a C. albicans strain, CaDBF4-02, with one CaDBF4 allele deleted and the other controlled by MET3 promoter that is methionine and cysteine repressible. Unexpectedly, CaDBF4 depleted strain remained in yeast form. Staggeringly, Southern blotting analysis of strain CaDBF4-02 revealed presence of three copies of CaDBF4 in C. albicans genome. Therefore, we constructed another C. albicans strain CaDBF4-0 from strain CaDBF4-02 in which the third DBF4 copy was knocked out. Similar to that of CaCDC7 depleted strain, we observed that the strain emerged hyphal form when the MET3 promoter was repressed. However, we were unable to obtain homozygous CaDBF4 null mutant. Hence, it is likely that CaDBF4 might be an essential gene. In addition, we constructed another C. albicans strain CaDBF4-05, with a plasmid integrated into the RP10 locus of the genome of strain CaDBF4-04 possessing an endogenous CaDBF4 whose expression is repressible by the control of MET3 promoter, which carries a copy of exogenous DBF4 capable of being expressed constitutively under the ACT1 promoter. We observed that cells of the strain CaDBF4-05 grew from yeast to the hyphal form by the expression of exogenous CaDBF4 when the endogenous CaDBF4 was repressed. Furthermore, constitutively expressing CaCDC7 in the strain CaDBF4-04 repressing CaDBF4 expression could not suppress hyphal growth. Therefore, we confirmed that CaDBF4, together with CaCDC7, is a negative regulator of hyphal formation.
From the above observations, we suggested presence of interaction between CaDBF4 and CaCDC7 in C. albicans, although functionally divergent from other eukaryotes. Interestingly, during the experimental process, we noted that C. albicans DBF4 gene with two heterologous alleles and the other allelic heterogeneity also exists in the C. albicans genome. Importantly, we determined that the third copy of DBF4 is inducibly duplicated by URA3-blaster.


中文摘要-----------------------------------------------------------------------------P.1
英文摘要-----------------------------------------------------------------------------P.4
1. 序論----------------------------------------------------------------------------P.7
1.1. 白色念珠菌與人類疾病-----------------------------------------------------P.7
1.2. 白色念珠菌的生物特性-----------------------------------------------------P.8
1.3. 白色念珠菌的生長形態-----------------------------------------------------P.9
1.3.1. 白色念珠菌的形態轉變-------------------------------------------------P.11
1.3.2. 白色念珠菌的形態轉變與細胞週期的關係-------------------------P.13
1.3.3. 形態轉變與致病力的關係----------------------------------------------P.14
1.4. DNA複製的起始------------------------------------------------------------P.16
1.4.1. Dbf4-dependent kinase複合體-------------------------------------------P.17
1.4.2. DDK的調節次單位DBF4 (Dumbbell Former 4)---------------------P.19
1.4.2.1. Dbf4-Motif-N Related to BRCT--------------------------------------P.20
1.4.2.2. Dbf4-Motif-M, a Proline-Rich Motif, Involved in
Protein-Protein Interaction-------------------------------------------------------P.20
1.4.2.3. Dbf4-Motif-C, a CCHH-Type Zinc Finger-like Motif-------------P.21
1.5. 研究動機---------------------------------------------------------------------P.23
2. 材料與方法---------------------------------------------------------------P.26
2.1. 大腸桿菌及白色念珠菌品系---------------------------------------------P.26
2.1.1. 大腸桿菌品系-------------------------------------------------------------P.26
2.1.2. 白色念珠菌品系----------------------------------------------------------P.26
2.2. 質體的建構------------------------------------------------------------------P.26
2.2.1. 載體(Vector)的製備------------------------------------------------------P.26
2.2.2. 插入DNA (Insert) 的製備----------------------------------------------P.27
2.2.3. 聚合酶連鎖反應 (Polymerase Chain Reaction)----------------------P.28
2.2.4. TA選殖----------------------------------------------------------------------P.29
2.2.5. 限制酶切割反應----------------------------------------------------------P.30
2.2.6. CIP的處理------------------------------------------------------------------P.31
2.2.7. 接合反應-------------------------------------------------------------------P.32
2.2.8. 以氯化鈣化學方法製備勝任細胞-------------------------------------P.32
2.2.9. 轉型作用(Transformation)----------------------------------------------P.33
2.2.10. 利用限制酶檢測質體的建構是否正確-----------------------------P.33
2.2.11. DNA定序------------------------------------------------------------------P.34
2.3. 白色念珠菌基因組的改造------------------------------------------------P.34
2.3.1. 白色念珠菌醋酸鋰轉殖法---------------------------------------------P.34
2.3.1.1. DNA片段的製備-------------------------------------------------------P.34
2.3.1.2. 醋酸鋰勝任細胞的製備----------------------------------------------P.34
2.3.1.3. 醋酸鋰轉殖法----------------------------------------------------------P.35
2.3.2. 白色念珠菌電穿孔轉殖法----------------------------------------------P.36
2.3.2.1. DNA片段的製備--------------------------------------------------------P.36
2.3.2.2. 電穿孔勝任細胞的製備----------------------------------------------P.36
2.3.2.3. 電穿孔轉殖法----------------------------------------------------------P.37
2.3.3. 5-Fluoroorotic Acid (5-FOA)的使用-----------------------------------P.37
2.3.4. Yeast colony PCR----------------------------------------------------------P.38
2.4. 南方點墨法------------------------------------------------------------------P.39
2.5. RT-PCR------------------------------------------------------------------------P.46
2.5.1. Total RNA的抽取---------------------------------------------------------P.46
2.5.2. Semi-quantitative RT-PCR-----------------------------------------------P.48
2.6. 蛋白質的萃取及定量------------------------------------------------------P.48
2.6.1. 蛋白質的萃取-------------------------------------------------------------P.48
2.6.2. 蛋白質的定量-------------------------------------------------------------P.49
2.7. 西方點墨法------------------------------------------------------------------P.50
2.7.1. SDS聚丙烯醯胺膠體電泳 (SDS-PAGE)-----------------------------P.50
2.7.2. 西方點墨法----------------------------------------------------------------P.51
2.8. 實驗中所使用的質體------------------------------------------------------P.53
2.8.1. pCR 2.1-TOPO-------------------------------------------------------------P.53
2.8.2. pFA-CaHIS-MET3p-------------------------------------------------------P.54
2.8.3. pbluescript (pBSII)--------------------------------------------------------P.54
2.8.4. pSFS1A---------------------------------------------------------------------P.54
2.8.5. p6HF-Act1------------------------------------------------------------------P.55
3. 結果--------------------------------------------------------------------------P.56
3.1. CaDbf4的胺基酸序列比對------------------------------------------------P.56
3.2. 白色念珠菌DBF4 DNA序列的比對------------------------------------P.56
3.3. 確認CaDBF4是否為必要基因以及CaDbf4耗盡時對白色念珠菌所
造成的影響------------------------------------------------------------------------P.57
3.3.1. 利用調控式的啟動子確認CaDBF4是否為必要基因--------------P.57
3.3.1.1. CaDBF4 URA3/+ (CaDBF4-01)的建構-----------------------------P.57
3.3.1.2. CaDBF4 MET3p/URA3 (CaDBF4-02)的建構---------------------P.58
3.3.1.3. 以yeast colony PCR 確認CaDBF4 URA3/+和CaDBF4
MET3p/URA3的基因組結構---------------------------------------------------P.60
3.3.1.4. 以Southern blotting確認CaDBF4-01和CaDBF4-02基因組結構
---------------------------------------------------------------------------------------P.61
3.3.1.5. 確認CaDBF4是否為必要基因---------------------------------------P.62
3.3.1.6. CaDBF4-02的形態觀察-----------------------------------------------P.62
3.3.2. 確認白色念珠菌DBF4有兩條對偶基因或兩條以上對偶基因--P.64
3.3.3. CaDBF4 MET3p/URA3/ARG4 (CaDBF4-03)的建構---------------P.66
3.3.3.1. 建構pBSII-DBF4-ARG4並送入CaDBF4-02-----------------------P.67
3.3.3.2. 以yeast colony PCR確認CaDBF4 MET3p/URA3/ARG4的基因組
結構---------------------------------------------------------------------------------P.68
3.3.3.3. 以Southern blotting確認CaDBF4-03的基因組結構--------------P.69
3.3.3.4. 確認DBF4是否為必要基因------------------------------------------P.70
3.3.3.5. CaDBF4-03的形態觀察-----------------------------------------------P.70
3.3.4. 確認白色念珠菌DBF4含有三條對偶基因--------------------------P.71
3.4. 建構CaDBF4 homozygous null 突變株--------------------------------P.72
3.4.1. CaDBF4 URA3/ARG4/+ (CaDBF4-10)的建構-----------------------P.72
3.4.2. CaDBF4 dpl200/ARG4/+ (CaDBF4-11)的建構----------------------P.73
3.4.3. CaDBF4 dpl200/AGR4/HIS1的建構-----------------------------------P.73
3.4.4. 以yeast colony PCR確認CaDBF4 URA3/ARG4/+和CaDBF4
dpl200/ARG4/+的基因組結構--------------------------------------------------P.74
3.4.5. 以Southern blotting確認CaDBF4-10和CaDBF4-11的基因組結構
---------------------------------------------------------------------------------------P.75
3.5. 以RT-PCR確認各strain的DBF4 mRNA表現量------------------------P.76
3.6. 確認CaDBF-03在抑制MET3啟動子的環境中所導致的形態變化為
內源性Dbf4耗盡造成的---------------------------------------------------------P.78
3.6.1. CaDBF4 MET3p/dpl200/ARG4 (CaDBF4-04)的建構--------------P.78
3.6.1.1. 5-FOA篩選--------------------------------------------------------------P.78
3.6.1.2. 以yeast colony PCR確認CaDBF4 MET3p/dpl200/ARG4的基因
組結構------------------------------------------------------------------------------P.78
3.6.1.3. 以Southern blotting確認CaDBF4-04的基因組結構--------------P.79
3.6.2. 利用持續性表現的ACT1啟動子將外源性CaDBF4於CaDBF4-04中
持續表現---------------------------------------------------------------------------P.79
3.6.2.1. 建構p6HF-Act1-DBF4並送入CaDBF4-04-------------------------P.79
3.6.2.2. 以yeast colony PCR確認p6HF-Act1-DBF4是否送入CaDBF4-04
的RP10基因座--------------------------------------------------------------------P.80
3.6.2.3. 以Southern blotting確認CaDBF4-05的基因組結構--------------P.81
3.6.3. 觀察CaDBF4-05持續表現外源性CaDBF4是否對形態轉變造成影
響------------------------------------------------------------------------------------P.81
3.7. 將一些與形態調控有關的基因在CaDBF4-04中持續表現,觀察是否
對形態造成影響------------------------------------------------------------------P.82
3.7.1. 利用持續性表現的ACT1啟動子將外源性CaCDC7於CaDBF4-04中
持續表現---------------------------------------------------------------------------P.82
3.7.2. 利用持續性表現的ACT1啟動子將外源性CaCDC4於CaDBF4-04
中持續表現------------------------------------------------------------------------P.83
3.7.3. 以yeast colony PCR確認p6HF-Act1、p6HF-Act1-CDC7和
p6HF-Act1-CDC4是否分別送入CaDBF4-04的RP10基因座-------------P.84
3.7.4. 以Southern blotting確認CaDBF4-06、CaDBF4-07和CaDBF4-09的基
因組結構是否正確---------------------------------------------------------------P.84

3.7.5. 觀察CaDBF4-04中持續表現外源性CaCDC7、CaCDC4是否對形態
轉變造成影響---------------------------------------------------------------------P.85
3.8. 利用螢光顯微鏡確認白色念珠菌各品系的形態---------------------P.86
3.8.1. 表現融合蛋白質CaCdc11-GFP於白色念珠菌中-------------------P.86
3.8.1.1. 建構p6HF-Act1-CDC11-GFP並送入CaDBF4-04----------------P.86
3.8.1.2. 以yeast colony PCR確認p6HF-Act1-CDC11-GFP是否送入
Ca-DBF4-04的RP10基因座-----------------------------------------------------P.87
3.8.1.3. 以Southern blotting確認CaDBF4-08的基因組結構是否正確
---------------------------------------------------------------------------------------P.87
3.8.1.4. 以western blotting確認融合蛋白質Cdc11-GFP有表現----------P.88
3.8.1.5. 以螢光顯微鏡觀察CaDBF4-08中Cdc11-GFP的表現------------P.88
3.9. 以SAT1 flipper系統剔除白色念珠菌的DBF4--------------------------P.89
3.9.1. CaDBF4 SAT1/+ (CaDBF4-12)的建構--------------------------------P.89
3.9.1.1. 建構pSFS1A-DBF4-UR-DR2並送入SC5314---------------------P.90
3.9.1.2. 利用yeast colony PCR確認CaDBF4 SAT1/+的基因組結構----P.91
3.9.1.3. 以Southern blotting確認CaDBF4-12的基因組結構--------------P.92
3.9.2. CaDBF4 FRT/+ (CaDBF4-13)的建構----------------------------------P.92
3.9.2.1. 剔除SAT1 marker-------------------------------------------------------P.92
3.9.2.2. 利用yeast colony PCR確認CaDBF4 FRT/+的基因組結構------P.93
3.9.2.3. 以Southern blotting確認CaDBF4-13的基因組結構--------------P.94
3.9.3. CaDBF4 SAT1/FRT的建構----------------------------------------------P.94
3.9.3.1. 建構pSFS1A-DBF4-UR2-DR並送入CaDBF4 SAT1/+----------P.94
3.10. 利用條件是剔除的方式建構白色念珠菌DBF4 homozygous null
mutation 的品系------------------------------------------------------------------P.96
3.10.1. 建構pSFS1A-DBF4-UR2-DR-ACT1P-DBF4並送入CaDBF4-13---
---------------------------------------------------------------------------------------P.96
3.10.2. 以yeast colony PCR確認CaDBF4-14的基因組結構-------------P.97
3.10.3. 外源性DBF4的剔除----------------------------------------------------P.98
3.11. 利用HIS1-blaster以及ARG4-blaster確認白色念珠菌BWP17的
DBF4對偶基因orf19.5166是否只會被URA3-blaster誘導而複製------P.99
3.11.1. 確認DBF4-URA3 (URA3-blaster)確實會使白色念珠菌DBF4對
偶基因orf19.5166複製----------------------------------------------------------P.99
3.11.2. 確認DBF4-HIS1 (HIS1-blaster)是否會使白色念珠菌DBF4對
偶基因orf19.5166複製---------------------------------------------------------P.100
3.11.3. 確認DBF4-ARG4 (ARG4-blaster)是否會使白色念珠菌DBF4對
偶基因orf19.5166複製---------------------------------------------------------P.100
4. 討論-------------------------------------------------------------------------P.101
4.1. Dbf4胺基酸序列比對----------------------------------------------------P.101
4.2. 三個DBF4對偶基因------------------------------------------------------P.102
4.3. Dbf4耗盡所造成之影響--------------------------------------------------P.104
4.4. DDK的原始功能-----------------------------------------------------------P.105
4.5. 細胞週期與形態轉變的關係--------------------------------------------P.107
4.6. 持續表現外源性CaCDC7與CaCDC4的影響------------------------P.109
4.7. 得不到DBF4 homozygous null突變株的討論-----------------------P.110

參考文獻----------------------------------------------------------------------P.167
附錄------------------------------------------------------------------------------P.171
表與圖
Table 1-----------------------------------------------------------------------------P.113
Table 2-----------------------------------------------------------------------------P.115
圖一、------------------------------------------------------------------------------P.118
圖二、------------------------------------------------------------------------------P.119
圖三、------------------------------------------------------------------------------P.120
圖四、------------------------------------------------------------------------------P.121
圖五、------------------------------------------------------------------------------P.122
圖六、------------------------------------------------------------------------------P.124
圖七、------------------------------------------------------------------------------P.125
圖八、------------------------------------------------------------------------------P.126
圖九、------------------------------------------------------------------------------P.127
圖十、------------------------------------------------------------------------------P.129
圖十一、---------------------------------------------------------------------------P.130
圖十二、---------------------------------------------------------------------------P.132圖十三、---------------------------------------------------------------------------P.133
圖十四、---------------------------------------------------------------------------P.134
圖十五、---------------------------------------------------------------------------P.136
圖十六、---------------------------------------------------------------------------P.137
圖十七、---------------------------------------------------------------------------P.139
圖十八、---------------------------------------------------------------------------P.141
圖十九、---------------------------------------------------------------------------P.143
圖二十、---------------------------------------------------------------------------P.145
圖二十一、------------------------------------------------------------------------P.147
圖二十二、------------------------------------------------------------------------P.148
圖二十三、------------------------------------------------------------------------P.149
圖二十四、------------------------------------------------------------------------P.150
圖二十五、------------------------------------------------------------------------P.151
圖二十六、------------------------------------------------------------------------P.153
圖二十七、------------------------------------------------------------------------P.155
圖二十八、------------------------------------------------------------------------P.156
圖二十九、------------------------------------------------------------------------P.157
圖三十、---------------------------------------------------------------------------P.159
圖三十一、------------------------------------------------------------------------P.161
圖三十二、------------------------------------------------------------------------P.163
圖三十三、------------------------------------------------------------------------P.164



Atir-Lande, A., Gildor, T., and Kornitzer, D. (2005). Role for the SCFCDC4 ubiquitin ligase in Candida albicans morphogenesis. Mol Biol Cell 16, 2772-2785.
Berman, J. (2006). Morphogenesis and cell cycle progression in Candida albicans. Curr Opin Microbiol 9, 595-601.
Berman, J., and Sudbery, P.E. (2002). Candida Albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet 3, 918-930.
Bernardo, S.M., Khalique, Z., Kot, J., Jones, J.K., and Lee, S.A. (2008). Candida albicans VPS1 contributes to protease secretion, filamentation, and biofilm formation. Fungal Genet Biol 45, 861-877.
Cannon, R.D., Lamping, E., Holmes, A.R., Niimi, K., Tanabe, K., Niimi, M., and Monk, B.C. (2007). Candida albicans drug resistance another way to cope with stress. Microbiology 153, 3211-3217.
Care, R.S., Trevethick, J., Binley, K.M., and Sudbery, P.E. (1999). The MET3 promoter: a new tool for Candida albicans molecular genetics. Mol Microbiol 34, 792-798.
Chen, S.C., and Sorrell, T.C. (2007). Antifungal agents. Med J Aust 187, 404-409.
Cheng, M.F., Yang, Y.L., Yao, T.J., Lin, C.Y., Liu, J.S., Tang, R.B., Yu, K.W., Fan, Y.H., Hsieh, K.S., Ho, M., et al. (2005). Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species. BMC Infect Dis 5, 22.
Cottier, F., and Muhlschlegel, F.A. (2009). Sensing the environment: response of Candida albicans to the X factor. FEMS Microbiol Lett 295, 1-9.
Crick, F.H. (1968). The origin of the genetic code. J Mol Biol 38, 367-379.
Douglas, L.M., Alvarez, F.J., McCreary, C., and Konopka, J.B. (2005). Septin function in yeast model systems and pathogenic fungi. Eukaryot Cell 4, 1503-1512.
Duncker, B.P., Shimada, K., Tsai-Pflugfelder, M., Pasero, P., and Gasser, S.M. (2002). An N-terminal domain of Dbf4p mediates interaction with both origin recognition complex (ORC) and Rad53p and can deregulate late origin firing. Proc Natl Acad Sci U S A 99, 16087-16092.
Forche, A., Alby, K., Schaefer, D., Johnson, A.D., Berman, J., and Bennett, R.J. (2008). The parasexual cycle in Candida albicans provides an alternative pathway to meiosis for the formation of recombinant strains. PLoS Biol 6, e110.
Francis, L.I., Randell, J.C., Takara, T.J., Uchima, L., and Bell, S.P. (2009). Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylation. Genes Dev 23, 643-654.


Gillum, A.M., Tsay, E.Y., and Kirsch, D.R. (1984). Isolation of the Candida albicans gene for orotidine-5''-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations. Mol Gen Genet 198, 179-182.
Harkins, V., Gabrielse, C., Haste, L., and Weinreich, M. (2009). Budding Yeast Dbf4 Sequences Required for Cdc7 Kinase Activation and Identification of a Functional Relationship Between the Dbf4 and Rev1 BRCT Domains. Genetics.
Heckman, D.S., Geiser, D.M., Eidell, B.R., Stauffer, R.L., Kardos, N.L., and Hedges, S.B. (2001). Molecular evidence for the early colonization of land by fungi and plants. Science 293, 1129-1133.
Kaneko, A., Umeyama, T., Hanaoka, N., Monk, B.C., Uehara, Y., and Niimi, M. (2004). Tandem affinity purification of the Candida albicans septin protein complex. Yeast 21, 1025-1033.
Kauffman, C.A. (2004). New antifungal agents. Semin Respir Crit Care Med 25, 233-239.
Kim, J.M., Kakusho, N., Yamada, M., Kanoh, Y., Takemoto, N., and Masai, H. (2008). Cdc7 kinase mediates Claspin phosphorylation in DNA replication checkpoint. Oncogene 27, 3475-3482.
Kumamoto, C.A., and Vinces, M.D. (2005). Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence. Cell Microbiol 7, 1546-1554.
Labib, K., and Gambus, A. (2007). A key role for the GINS complex at DNA replication forks. Trends Cell Biol 17, 271-278.
Lei, M., and Tye, B.K. (2001). Initiating DNA synthesis: from recruiting to activating the MCM complex. J Cell Sci 114, 1447-1454.
Marston, A.L. (2009). Meiosis: DDK is not just for replication. Curr Biol 19, R74-76.
Masai, H., and Arai, K. (2000). Dbf4 motifs: conserved motifs in activation subunits for Cdc7 kinases essential for S-phase. Biochem Biophys Res Commun 275, 228-232.
Masai, H., and Arai, K. (2002). Cdc7 kinase complex: a key regulator in the initiation of DNA replication. J Cell Physiol 190, 287-296.
Masia Canuto, M., and Gutierrez Rodero, F. (2002). Antifungal drug resistance to azoles and polyenes. Lancet Infect Dis 2, 550-563.
Michel, S., Ushinsky, S., Klebl, B., Leberer, E., Thomas, D., Whiteway, M., and Morschhauser, J. (2002). Generation of conditional lethal Candida albicans mutants by inducible deletion of essential genes. Mol Microbiol 46, 269-280.
Morgan, J. (2005). Global trends in candidemia: review of reports from 1995-2005. Curr Infect Dis Rep 7, 429-439.
Moyer, S.E., Lewis, P.W., and Botchan, M.R. (2006). Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A 103, 10236-10241.
Noble, S.M., French, S., Kohn, L.A., Chen, V., and Johnson, A.D. Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet 42, 590-598.
Ogi, H., Wang, C.Z., Nakai, W., Kawasaki, Y., and Masumoto, H. (2008). The role of the Saccharomyces cerevisiae Cdc7-Dbf4 complex in the replication checkpoint. Gene 414, 32-40.
Parker, J.C., Jr., McCloskey, J.J., and Knauer, K.A. (1976). Pathobiologic features of human candidiasis. A common deep mycosis of the brain, heart and kidney in the altered host. Am J Clin Pathol 65, 991-1000.
Reuss, O., Vik, A., Kolter, R., and Morschhauser, J. (2004). The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene 341, 119-127.
Santos, M.A., and Tuite, M.F. (1995). The CUG codon is decoded in vivo as serine and not leucine in Candida albicans. Nucleic Acids Res 23, 1481-1486.
Schaub, Y., Dunkler, A., Walther, A., and Wendland, J. (2006). New pFA-cassettes for PCR-based gene manipulation in Candida albicans. J Basic Microbiol 46, 416-429.
Stillman, B. (2005). Origin recognition and the chromosome cycle. FEBS Lett 579, 877-884.
Su, Z., Li, H., Li, Y., and Ni, F. (2007). Inhibition of the pathogenically related morphologic transition in Candida albicans by disrupting Cdc42 binding to its effectors. Chem Biol 14, 1273-1282.
Sudbery, P., Gow, N., and Berman, J. (2004). The distinct morphogenic states of Candida albicans. Trends Microbiol 12, 317-324.
Tsuji, T., Lau, E., Chiang, G.G., and Jiang, W. (2008). The role of Dbf4/Drf1-dependent kinase Cdc7 in DNA-damage checkpoint control. Mol Cell 32, 862-869.
Varrin, A.E., Prasad, A.A., Scholz, R.P., Ramer, M.D., and Duncker, B.P. (2005). A mutation in Dbf4 motif M impairs interactions with DNA replication factors and confers increased resistance to genotoxic agents. Mol Cell Biol 25, 7494-7504.
Viudes, A., Peman, J., Canton, E., Ubeda, P., Lopez-Ribot, J.L., and Gobernado, M. (2002). Candidemia at a tertiary-care hospital: epidemiology, treatment, clinical outcome and risk factors for death. Eur J Clin Microbiol Infect Dis 21, 767-774.
Walia, A., and Calderone, R. (2008). The SSK2 MAPKKK of Candida albicans is required for oxidant adaptation in vitro. FEMS Yeast Res 8, 287-299
Wan, L., Niu, H., Futcher, B., Zhang, C., Shokat, K.M., Boulton, S.J., and Hollingsworth, N.M. (2008). Cdc28-Clb5 (CDK-S) and Cdc7-Dbf4 (DDK) collaborate to initiate meiotic recombination in yeast. Genes Dev 22, 386-397.
Whiteway, M., and Bachewich, C. (2007). Morphogenesis in Candida albicans. Annu Rev Microbiol 61, 529-553.
Whiteway, M., and Oberholzer, U. (2004). Candida morphogenesis and host-pathogen interactions. Curr Opin Microbiol 7, 350-357.
Wilson, L.S., Reyes, C.M., Stolpman, M., Speckman, J., Allen, K., and Beney, J. (2002). The direct cost and incidence of systemic fungal infections. Value Health 5, 26-34.
Wysong, D.R., Christin, L., Sugar, A.M., Robbins, P.W., and Diamond, R.D. (1998). Cloning and sequencing of a Candida albicans catalase gene and effects of disruption of this gene. Infect Immun 66, 1953-1961.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
1. 沈惠如:〈李漁家伶演劇研究〉,《德育學報》,第8期,1992年10月,頁119-128。
2. 李惠綿:〈明代戲曲文律論之開展演變〉,《臺大中文學報》,第20期,2004年6月,頁135-19。
3. 張薰:〈李漁「窺詞管見」析論〉,《致理學報》,第19期,2004年11月,頁99-128。
4. 李惠綿:〈李漁劇作中的神異情節〉,《中國文學研究》,第5期,1991年5月,頁277-302。
5. 張敬:〈論李笠翁十種曲〉,《幼獅文藝》,第41卷第5期,1975年5月,頁139-162。
6. 范民仁:〝An Evaluation of Li Yu''s Revised Scene of P''I-P''A Chi--With Reference to His Theory of Drama〞,《源遠學報》,第2期,1989年11月,頁19-25。
7. 吳淑慧:〈明清傳奇教化典範的思索──以李漁《閒情偶寄》對戲曲典範的再理解〉,《輔大中研所學刊》,第11期,2001年10月,頁255-270。
8. 王璦玲:〈晚明清初戲曲審美意識中情理觀之轉化及其意義〉,《中國文哲研究集刊》,第19期,2001年9月,頁。183-250
9. 王璦玲:〈明末清初才子佳人劇之言情內涵及其所引生之審美構思〉,《中國文哲研究集刊》,第18期,2001年3月,頁139-188。
10. 王建科:〈李漁的科諢理論及其小說戲曲的科諢藝術〉,《東方人文學誌》,第1卷第4期,2002年12月,頁123-147。
11. 黃雅莉:〈李漁《窺詞管見》淺析〉,《語文學報》,第12期,2005年12月,頁57-85。
12. 詹皓宇:〈書寫才女--李漁〈喬復生王再來二姬合傳〉評析〉,《東方人文學誌》,第8卷第4期,2009年12月,頁173-190。
13. 劉慧珠:〈李漁文學觀中的虛實論〉,《修平學報》,第5期,2002年9月,頁87-107。
14. 賴慧玲:〈李漁喜劇「笑點」的語用前題分析--以「風箏誤」、「蜃中樓」、「奈何天」為例〉,《東海中文學報》,第11期,1994年12月,頁121-129。
15. 賴慧玲:〈從李漁的「科諢論」看他的三部喜劇--「風箏誤」「蜃中樓」「奈何天」〉,《興大中文學報》,第6期,1993年1月,頁267-282。
 
系統版面圖檔 系統版面圖檔