成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	許嘉麟 Shiu, Jia-Lin
論文名稱：	HLTF與PARP1交互作用促使損傷複製叉的進展和穩定性以賦予化學抗藥性 The HLTF-PARP1 interaction promotes the progression and stability of damage replication forks to confer chemoresistance
指導教授：	廖泓鈞 Liaw, Hung-Jiun
學位類別：	博士 Doctor
系所名稱：	生物科學與科技學院 - 生命科學系 Department of Life Sciences
論文出版年：	2021
畢業學年度：	109
語文別：	英文
論文頁數：	88
中文關鍵詞：	HLTF 、PARP1 、複製叉反轉、模板置換、同源重組
外文關鍵詞：	HLTF, PARP1, Fork reversal, template switching, homologous recombination
相關次數：	點閱：162 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

中文摘要 (Abstract in Chinese)	I
Abstract	II
誌謝 (Acknowledgements)	III
Content	IV
Abbreviations list	VIII
Chapter 1 Introduction	1
1-1. DNA damage response (DDR)	1
1-2. Genome instability	2
1-3. Mutator phenotype hypothesis and tumorigenesis 	3
1-4. Post-replication repair (PRR)	3
1-5. The function of Helicase-like transcription factor (HLTF) 	4
1-6. The function of Poly (ADP-ribose) polymerase 1 (PARP1)	5
1-7. Homologous recombination (HR)	7
1-8. Fork stabilization, protection, reversal, and restart	8
1-9. Aim of this study	11
Chapter 2 Material and Methods	12
2-1. Cell culture	12
2-2. RNA interference	12
2-3. The generation of HLTF and PARP1 knockout HONE6 clones by CRISPR-Cas9	12
2-4. EdU-PLA assay	13
2-5. Plasmid construction	14
2-6. Western blotting	14
2-7. Co-immunoprecipitation (CoIP)	15
2-8. GST pulldown assay	16
2-9. DNA fiber analysis	16
2-10. Immunofluorescence microscopy	17
2-11. Sister chromatid exchange (SCE) 	18
2-12. Colony formation assay 	18
2-13. Cytotoxicity assay	19
Chapter 3 Results	20
3-1. Cisplatin-resistant HONE6 and HONE15 cells are resistant to various DNA damaging agents	20
3-2. Cisplatin-resistant HONE6 cells bypass more DNA lesions than HONE1 cells with MMS treatment	21
3-3. HLTF interacts with PARP1	22
3-4. Both HLTF and PARP1 interact with BARD1	23
3-5. TS and HR proteins are enriched at stalled replication forks	25
3-6. The kinetics of PARP1 and HLTF at damaged forks alters in the HLTF and PARP1 knockout cells	27
3-7. Depletion of HLTF, UBC13, BARD1, and PARP1 decreases the replication fork progression in response to MMS and UV irradiation treatment	29
3-8. Depletion of HLTF, UBC13, BARD1, and PARP1 increases DSBs in response to MMS- induced DNA lesions	31
3-9. Depletion of HLTF, BRCA1, and BARD1 reduces the levels of RAD51 at stalled forks	32
3-10. The depletion of HLTF, UBC13, BARD1, and PARP1 sensitizes cells to cisplatin, MMS, and 4NQO treatment	33
Chapter 4 Discussion and Conclusion	35
References	42
Figures and Tables	54
Figure 1. The cisplatin-resistant NPC cells, HONE6 and HONE15 cells, are resistant to DNA damage agents.	54
Figure 2. Cisplatin-resistant HONE6 and HONE15 cells show elevated frequencies of sister chromatid exchange (SCE).	55
Figure 3. PRR and HR genes of cisplatin-resistant HONE6 and HONE15 cells are overexpression.	56
Figure 4. Cisplatin-resistant HONE6 cells show longer replication tracks than HONE1 cells upon MMS treatment.	58
Figure 5. HLTF interacts with PARP1 and BARD1.	60
Figure 6. HLTF, PARP1, and BARD1 interact with each other in vivo.	61
Figure 7. HLTF, PARP1, BARD1, UBC13, and PCNA accumulate at damaged forks.	63
Figure 8. The kinetics of PARP1 and HLTF at damaged forks in the HLTF-KO and PARP1-KO cells.  	65
Figure 9. Depletion of HLTF, UBC13, BARD1, or PARP1 significantly decreases replication tracks and increases stalled replication forks in HONE6 cells.	68
Figure 10. MMS causes more DSBs in HLTF, PARP1, BARD1, and UBC13-depleted HONE6 cells.	70
Figure 11. Sister chromatid exchange in HLTF-, PARP1-, BARD1-, and UBC13- depleted HONE6 cells.	72
Figure 12. The RAD51/EdU PLA foci at damaged forks in the HLTF-, BRCA1-, BARD1-, and PARP1-depleted HONE6 cells.	74
Figure 13. Depletion of HLTF, UBC13, BARD1, and PARP1 sensitizes HONE6 cells to cisplatin, MMS and 4NQO.	77
Figure 14. HLTF-KO and PARP1-KO T24 cells are more sensitive to MMS than wild-type cells.	78
Figure 15. The protein stability of HLTF and PARP1 is in wild-type, HLTF-KO, and PARP1-KO HONE6 cells.	79
Figure 16. The PARP1-HLTF interaction in the presence of olaparib.	80
Figure 17. The levels of PCNA ubiquitination are reduced in the HLTF-KO and PARP1-KO cells.	81
Figure 18. Schematic model for the function of HLTF, PARP1, and HR proteins in the TS pathway.	82
Table 1. The list of targeting sequences of shRNA used in this study.	83
Table 2. The list of antibodies used in this study.	84
Appendix figure 1. HLTF-KO and PARP1-KO HONE6 cells show higher levels of γH2AX than wild-type control cells.	85
Appendix figure 2. γH2AX and 53BP1 foci are highly correlated upon MMS treatment.	86
Appendix figure 3. The RAD51/EdU PLA foci at damaged forks in the HLTF-KO and PARP1-KO HONE6 cells.	87
Appendix figure 4. HLTF localizes both in cytoplasm and nucleus, and PARP1 localizes only in nucleus.	88
                                    

1 Ciccia, A. & Elledge, S. J. The DNA damage response: making it safe to play with knives. Mol Cell 40, 179-204 (2010).
2 Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K. & Linn, S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73, 39-85 (2004).
3 Houtgraaf, J. H., Versmissen, J. & van der Giessen, W. J. A concise review of DNA damage checkpoints and repair in mammalian cells. Cardiovascular revascularization medicine : including molecular interventions 7, 165-172 (2006).
4 Petrini, J. H. & Stracker, T. H. The cellular response to DNA double-strand breaks: defining the sensors and mediators. Trends Cell Biol 13, 458-462 (2003).
5 Asimuddin, M. & Jamil, K. Insight into the DNA repair mechanism operating during cell cycle checkpoints in eukaryotic cells. Biology and Medicine 4, 147 (2012).
6 Zhou, B. B. & Elledge, S. J. The DNA damage response: putting checkpoints in perspective. Nature 408, 433-439 (2000).
7 Nyberg, K. A., Michelson, R. J., Putnam, C. W. & Weinert, T. A. Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 36, 617-656 (2002).
8 Abraham, R. T. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & development 15, 2177-2196 (2001).
9 Storchova, Z. & Pellman, D. From polyploidy to aneuploidy, genome instability and cancer. Nature reviews. Molecular cell biology 5, 45-54 (2004).
10 Gao, C. et al. Chromosome instability, chromosome transcriptome, and clonal evolution of tumor cell populations. Proceedings of the National Academy of Sciences of the United States of America 104, 8995-9000 (2007).
11 Cimprich, K. A. & Cortez, D. ATR: an essential regulator of genome integrity. Nature reviews. Molecular cell biology 9, 616-627 (2008).
12 Cortez, D., Wang, Y., Qin, J. & Elledge, S. J. Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286, 1162-1166 (1999).
13 Kolodner, R. D., Putnam, C. D. & Myung, K. Maintenance of genome stability in Saccharomyces cerevisiae. Science 297, 552-557 (2002).
14 Scully, R. & Livingston, D. M. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 408, 429-432 (2000).
15 Motegi, A. et al. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proceedings of the National Academy of Sciences of the United States of America 105, 12411-12416 (2008).
16 Motegi, A. et al. Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. The Journal of cell biology 175, 703-708 (2006).
17 Loeb, L. A., Loeb, K. R. & Anderson, J. P. Multiple mutations and cancer. Proceedings of the National Academy of Sciences of the United States of America 100, 776-781 (2003).
18 Jackson, A. L., Newcomb, T. G. & Loeb, L. A. Origin of multiple mutations in human cancers. Drug metabolism reviews 30, 285-304 (1998).
19 Loeb, L. A. A mutator phenotype in cancer. Cancer Res 61, 3230-3239 (2001).
20 Loeb, L. A. Human cancers express mutator phenotypes: origin, consequences and targeting. Nature reviews. Cancer 11, 450-457 (2011).
21 Loeb, L. A., Bielas, J. H. & Beckman, R. A. Cancers exhibit a mutator phenotype: clinical implications. Cancer Res 68, 3551-3557; discussion 3557 (2008).
22 Bray, C. M. & West, C. E. DNA repair mechanisms in plants: crucial sensors and effectors for the maintenance of genome integrity. The New phytologist 168, 511-528 (2005).
23 Loeb, L. A., Springgate, C. F. & Battula, N. Errors in DNA replication as a basis of malignant changes. Cancer research 34, 2311-2321 (1974).
24 Heller, R. C. & Marians, K. J. Replisome assembly and the direct restart of stalled replication forks. Nature reviews. Molecular cell biology 7, 932-943 (2006).
25 Ulrich, H. D. The RAD6 pathway: control of DNA damage bypass and mutagenesis by ubiquitin and SUMO. Chembiochem 6, 1735-1743 (2005).
26 Kannouche, P. L., Wing, J. & Lehmann, A. R. Interaction of human DNA polymerase η with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage. Molecular cell 14, 491-500 (2004).
27 Chang, D. J. & Cimprich, K. A. DNA damage tolerance: when it's OK to make mistakes. Nature chemical biology 5, 82-90 (2009).
28 Ghosal, G. & Chen, J. DNA damage tolerance: a double-edged sword guarding the genome. Transl Cancer Res 2, 107-129 (2013).
29 Niimi, A. et al. Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 105, 16125-16130 (2008).
30 Tian, F. et al. BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade. Proceedings of the National Academy of Sciences of the United States of America 110, 13558-13563 (2013).
31 Prakash, S., Johnson, R. E. & Prakash, L. Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem 74, 317-353 (2005).
32 Ogi, T., Shinkai, Y., Tanaka, K. & Ohmori, H. Polκ protects mammalian cells against the lethal and mutagenic effects of benzo [a] pyrene. Proceedings of the National Academy of Sciences 99, 15548-15553 (2002).
33 Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S. & Prakash, L. Eukaryotic polymerases ι and ζ act sequentially to bypass DNA lesions. Nature 406, 1015-1019 (2000).
34 Johnson, R. E., Prakash, S. & Prakash, L. Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Polη. Science 283, 1001-1004 (1999).
35 Bienko, M. et al. Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis. Science 310, 1821-1824 (2005).
36 Sale, J. E. Translesion DNA synthesis and mutagenesis in eukaryotes. Cold Spring Harb Perspect Biol 5, a012708 (2013).
37 Waters, L. S. et al. Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance. Microbiology and Molecular Biology Reviews 73, 134-154 (2009).
38 Burkovics, P., Sebesta, M., Balogh, D., Haracska, L. & Krejci, L. Strand invasion by HLTF as a mechanism for template switch in fork rescue. Nucleic acids research 42, 1711-1720 (2014).
39 Unk, I. et al. Human SHPRH is a ubiquitin ligase for Mms2–Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Proceedings of the National Academy of Sciences 103, 18107-18112 (2006).
40 Petermann, E. & Helleday, T. Pathways of mammalian replication fork restart. Nature reviews. Molecular cell biology 11, 683-687 (2010).
41 San Filippo, J., Sung, P. & Klein, H. Mechanism of eukaryotic homologous recombination. Annu Rev Biochem 77, 229-257 (2008).
42 Minca, E. C. & Kowalski, D. Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks. Molecular cell 38, 649-661 (2010).
43 Debauve, G., Capouillez, A., Belayew, A. & Saussez, S. The helicase-like transcription factor and its implication in cancer progression. Cellular and molecular life sciences : CMLS 65, 591-604 (2008).
44 Blastyák, A., Hajdú, I., Unk, I. & Haracska, L. Role of double-stranded DNA translocase activity of human HLTF in replication of damaged DNA. Molecular and cellular biology 30, 684-693 (2010).
45 Achar, Y. J., Balogh, D. & Haracska, L. Coordinated protein and DNA remodeling by human HLTF on stalled replication fork. Proceedings of the National Academy of Sciences of the United States of America 108, 14073-14078 (2011).
46 Achar, Y. J. et al. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling. Nucleic Acids Res 43, 10277-10291 (2015).
47 Kile, A. C. et al. HLTF’s ancient HIRAN domain binds 3′ DNA ends to drive replication fork reversal. Molecular cell 58, 1090-1100 (2015).
48 Zellweger, R. et al. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. Journal of Cell Biology 208, 563-579 (2015).
49 Kolinjivadi, A. M. et al. Smarcal1-Mediated Fork Reversal Triggers Mre11-Dependent Degradation of Nascent DNA in the Absence of Brca2 and Stable Rad51 Nucleofilaments. Mol Cell 67, 867-881 e867 (2017).
50 Ciccia, A. et al. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol Cell 47, 396-409 (2012).
51 Bétous, R. et al. Substrate-selective repair and restart of replication forks by DNA translocases. Cell reports 3, 1958-1969 (2013).
52 Bétous, R. et al. SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication. Genes & development 26, 151-162 (2012).
53 Vujanovic, M. et al. Replication fork slowing and reversal upon DNA damage require PCNA polyubiquitination and ZRANB3 DNA translocase activity. Molecular cell 67, 882-890. e885 (2017).
54 Chen, S., Davies, A. A., Sagan, D. & Ulrich, H. D. The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner. Nucleic Acids Res 33, 5878-5886 (2005).
55 Ding, H. et al. Characterization of a helicase-like transcription factor involved in the expression of the human plasminogen activator inhibitor-1 gene. DNA Cell Biol 15, 429-442 (1996).
56 Sheridan, P. L., Schorpp, M., Voz, M. L. & Jones, K. A. Cloning of an SNF2/SWI2-related Protein That Binds Specifically to the SPH Motifs of the SV40 Enhancer and to the HIV-1 Promoter (∗). Journal of Biological Chemistry 270, 4575-4587 (1995).
57 Mohrmann, L. & Verrijzer, C. P. Composition and functional specificity of SWI2/SNF2 class chromatin remodeling complexes. Biochimica et biophysica acta 1681, 59-73 (2005).
58 Tang, L., Nogales, E. & Ciferri, C. Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription. Prog Biophys Mol Biol 102, 122-128 (2010).
59 Moinova, H. R. et al. HLTF gene silencing in human colon cancer. Proceedings of the National Academy of Sciences of the United States of America 99, 4562-4567 (2002).
60 Hamai, Y. et al. DNA hypermethylation and histone hypoacetylation of the HLTF gene are associated with reduced expression in gastric carcinoma. Cancer Sci 94, 692-698 (2003).
61 Fukuoka, T., Hibi, K. & Nakao, A. Aberrant methylation is frequently observed in advanced esophageal squamous cell carcinoma. Anticancer research 26, 3333-3335 (2006).
62 Kang, S. et al. Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma. Int J Cancer 118, 2168-2171 (2006).
63 Debauve, G. et al. Early expression of the Helicase-Like Transcription Factor (HLTF/SMARCA3) in an experimental model of estrogen-induced renal carcinogenesis. Mol Cancer 5, 23 (2006).
64 Schmitt, M. et al. Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 78, 285-296 (1997).
65 Li, N. & Chen, J. ADP-ribosylation: activation, recognition, and removal. Mol Cells 37, 9-16 (2014).
66 Parsons, J. L., Dianova, II, Allinson, S. L. & Dianov, G. L. Poly(ADP-ribose) polymerase-1 protects excessive DNA strand breaks from deterioration during repair in human cell extracts. FEBS J 272, 2012-2021 (2005).
67 Fisher, A. E., Hochegger, H., Takeda, S. & Caldecott, K. W. Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase. Mol Cell Biol 27, 5597-5605 (2007).
68 Ali, A. A. E. et al. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks. Nat Struct Mol Biol 19, 685-692 (2012).
69 Haince, J.-F. et al. Ataxia telangiectasia mutated (ATM) signaling network is modulated by a novel poly (ADP-ribose)-dependent pathway in the early response to DNA-damaging agents. Journal of Biological Chemistry 282, 16441-16453 (2007).
70 Kraus, W. L. Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation. Curr Opin Cell Biol 20, 294-302 (2008).
71 Li, B., Navarro, S., Kasahara, N. & Comai, L. Identification and biochemical characterization of a Werner's syndrome protein complex with Ku70/80 and poly(ADP-ribose) polymerase-1. The Journal of biological chemistry 279, 13659-13667 (2004).
72 Hu, Y. et al. PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination–mediated DNA repair. Cancer discovery 4, 1430-1447 (2014).
73 Hassa, P. O., Haenni, S. S., Elser, M. & Hottiger, M. O. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? Microbiology and Molecular Biology Reviews 70, 789-829 (2006).
74 Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H. & Poirier, G. G. PARP inhibition: PARP1 and beyond. Nature reviews. Cancer 10, 293-301 (2010).
75 Hassa, P. O. & Hottiger, M. O. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci 13, 3046-3082 (2008).
76 Schreiber, V., Dantzer, F., Ame, J. C. & de Murcia, G. Poly(ADP-ribose): novel functions for an old molecule. Nature reviews. Molecular cell biology 7, 517-528 (2006).
77 Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917-921 (2005).
78 Bryant, H. E. et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434, 913-917 (2005).
79 Patel, A. G., Sarkaria, J. N. & Kaufmann, S. H. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proceedings of the National Academy of Sciences of the United States of America 108, 3406-3411 (2011).
80 Schreiber, V. et al. Poly (ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. Journal of Biological Chemistry 277, 23028-23036 (2002).
81 de Murcia, J. M. et al. Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse. The EMBO journal 22, 2255-2263 (2003).
82 Krishnakumar, R. & Kraus, W. L. The PARP side of the nucleus: molecular actions, physiological outcomes, and clinical targets. Mol Cell 39, 8-24 (2010).
83 Luo, X. & Kraus, W. L. On PAR with PARP: cellular stress signaling through poly (ADP-ribose) and PARP-1. Genes & development 26, 417-432 (2012).
84 Pfeiffer, P., Goedecke, W. & Obe, G. Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations. Mutagenesis 15, 289-302 (2000).
85 O'Driscoll, M. & Jeggo, P. A. The role of double-strand break repair—insights from human genetics. Nature Reviews Genetics 7, 45-54 (2006).
86 Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S. & Bonner, W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. The Journal of biological chemistry 273, 5858-5868 (1998).
87 Lavin, M. F. et al. ATM signaling and genomic stability in response to DNA damage. Mutation research 569, 123-132 (2005).
88 Chen, L., Nievera, C. J., Lee, A. Y.-L. & Wu, X. Cell cycle-dependent complex formation of BRCA1· CtIP· MRN is important for DNA double-strand break repair. Journal of Biological Chemistry 283, 7713-7720 (2008).
89 Yu, X. & Chen, J. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol 24, 9478-9486 (2004).
90 Huertas, P. & Jackson, S. P. Human CtIP mediates cell cycle control of DNA end resection and double strand break repair. The Journal of biological chemistry 284, 9558-9565 (2009).
91 Bekker-Jensen, S. et al. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol 173, 195-206 (2006).
92 Sung, P., Krejci, L., Van Komen, S. & Sehorn, M. G. Rad51 recombinase and recombination mediators. The Journal of biological chemistry 278, 42729-42732 (2003).
93 Liu, Y. & West, S. C. Happy Hollidays: 40th anniversary of the Holliday junction. Nature reviews. Molecular cell biology 5, 937-944 (2004).
94 Esteller, M. et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. Journal of the National Cancer Institute 92, 564-569 (2000).
95 Russell, P. A. et al. Frequent loss of BRCA1 mRNA and protein expression in sporadic ovarian cancers. Int J Cancer 87, 317-321 (2000).
96 Thompson, M. E., Jensen, R. A., Obermiller, P. S., Page, D. L. & Holt, J. T. Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression. Nature genetics 9, 444-450 (1995).
97 Wilson, C. A. et al. Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 21, 236-240 (1999).
98 Chapman, J. R., Taylor, M. R. & Boulton, S. J. Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47, 497-510 (2012).
99 O'Donovan, P. J. & Livingston, D. M. BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 31, 961-967 (2010).
100 Gudmundsdottir, K. & Ashworth, A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 25, 5864-5874 (2006).
101 Moynahan, M. E. & Jasin, M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nature reviews. Molecular cell biology 11, 196-207 (2010).
102 Wray, J., Liu, J., Nickoloff, J. A. & Shen, Z. Distinct RAD51 associations with RAD52 and BCCIP in response to DNA damage and replication stress. Cancer Res 68, 2699-2707 (2008).
103 Bunting, S. F. et al. BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair. Mol Cell 46, 125-135, (2012).
104 Byun, T. S., Pacek, M., Yee, M. C., Walter, J. C. & Cimprich, K. A. Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. Genes Dev 19, 1040-1052 (2005).
105 Kottemann, M. C., Conti, B. A., Lach, F. P. & Smogorzewska, A. Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity. Mol Cell 69, 24-35 e25 (2018).
106 Binz, S. K., Sheehan, A. M. & Wold, M. S. Replication protein A phosphorylation and the cellular response to DNA damage. DNA Repair (Amst) 3, 1015-1024 (2004).
107 Fan, J. & Pavletich, N. P. Structure and conformational change of a replication protein A heterotrimer bound to ssDNA. Genes Dev 26, 2337-2347 (2012).
108 Fanning, E., Klimovich, V. & Nager, A. R. A dynamic model for replication protein A (RPA) function in DNA processing pathways. Nucleic Acids Res 34, 4126-4137 (2006).
109 Chen, R. & Wold, M. S. Replication protein A: single‐stranded DNA's first responder: dynamic DNA‐interactions allow replication protein A to direct single‐strand DNA intermediates into different pathways for synthesis or repair. Bioessays 36, 1156-1161 (2014).
110 Iyer, D. R. & Rhind, N. The Intra-S Checkpoint Responses to DNA Damage. Genes (Basel) 8, 74 (2017).
111 Syljuåsen, R. G. et al. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Molecular and cellular biology 25, 3553-3562 (2005).
112 Petermann, E., Woodcock, M. & Helleday, T. Chk1 promotes replication fork progression by controlling replication initiation. Proceedings of the National Academy of Sciences of the United States of America 107, 16090-16095 (2010).
113 Shechter, D., Costanzo, V. & Gautier, J. ATR and ATM regulate the timing of DNA replication origin firing. Nat Cell Biol 6, 648-655 (2004).
114 Poole, L. A. & Cortez, D. Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability. Crit Rev Biochem Mol Biol 52, 696-714 (2017).
115 Liao, H., Ji, F., Helleday, T. & Ying, S. Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments. EMBO Rep 19, e46263 (2018).
116 Ciccia, A. et al. The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart. Genes & development 23, 2415-2425 (2009).
117 Ralf, C., Hickson, I. D. & Wu, L. The Bloom's syndrome helicase can promote the regression of a model replication fork. Journal of biological chemistry 281, 22839-22846 (2006).
118 Bansbach, C. E., Bétous, R., Lovejoy, C. A., Glick, G. G. & Cortez, D. The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks. Genes & development 23, 2405-2414 (2009).
119 Unk, I. et al. Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear antigen polyubiquitination. Proceedings of the National Academy of Sciences 105, 3768-3773 (2008).
120 Gari, K., Decaillet, C., Delannoy, M., Wu, L. & Constantinou, A. Remodeling of DNA replication structures by the branch point translocase FANCM. Proceedings of the National Academy of Sciences of the United States of America 105, 16107-16112 (2008).
121 Fugger, K. et al. FBH1 Catalyzes Regression of Stalled Replication Forks. Cell Rep 10, 1749-1757 (2015).
122 Collis, S. J. et al. FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex. Mol Cell 32, 313-324 (2008).
123 Chaudhuri, A. R. et al. Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Nature structural & molecular biology 19, 417-423 (2012).
124 Berti, M. et al. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat Struct Mol Biol 20, 347-354 (2013).
125 Schlacher, K. et al. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell 145, 529-542 (2011).
126 Schlacher, K., Wu, H. & Jasin, M. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell 22, 106-116 (2012).
127 Michl, J., Zimmer, J., Buffa, F. M., McDermott, U. & Tarsounas, M. FANCD2 limits replication stress and genome instability in cells lacking BRCA2. Nat Struct Mol Biol 23, 755-757 (2016).
128 Chaudhuri, A. R. et al. Erratum: Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature 539, 456 (2016).
129 Lemaçon, D. et al. MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nature communications 8, 1-12 (2017).
130 Mijic, S. et al. Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nat Commun 8, 859 (2017).
131 Ding, X. et al. Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies. Nat Commun 7, 12425 (2016).
132 Su, W. P. et al. Chronic treatment with cisplatin induces replication-dependent sister chromatid recombination to confer cisplatin-resistant phenotype in nasopharyngeal carcinoma. Oncotarget 5, 6323-6337 (2014).
133 Li, M., Lu, L. Y., Yang, C. Y., Wang, S. & Yu, X. The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response. Genes Dev 27, 1752-1768 (2013).
134 Li, M. & Yu, X. Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. Cancer cell 23, 693-704 (2013).
135 Beranek, D. T. Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. Mutation research 231, 11-30 (1990).
136 Ensminger, M. et al. DNA breaks and chromosomal aberrations arise when replication meets base excision repair. Journal of Cell Biology 206, 29-43 (2014).
137 Petruk, S. et al. TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell 150, 922-933 (2012).
138 Roy, S., Luzwick, J. W. & Schlacher, K. SIRF: Quantitative in situ analysis of protein interactions at DNA replication forks. Journal of Cell Biology 217, 1521-1536 (2018).
139 Lin, J. R., Zeman, M. K., Chen, J. Y., Yee, M. C. & Cimprich, K. A. SHPRH and HLTF act in a damage-specific manner to coordinate different forms of postreplication repair and prevent mutagenesis. Mol Cell 42, 237-249 (2011).
140 Branzei, D., Vanoli, F. & Foiani, M. SUMOylation regulates Rad18-mediated template switch. Nature 456, 915-920 (2008).
141 Hoege, C., Pfander, B., Moldovan, G.-L., Pyrowolakis, G. & Jentsch, S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419, 135-141 (2002).
142 Suzuka, I. et al. Gene for proliferating-cell nuclear antigen (DNA polymerase delta auxiliary protein) is present in both mammalian and higher plant genomes. Proceedings of the National Academy of Sciences 86, 3189-3193 (1989).
143 Alabert, C. et al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol 16, 281-293 (2014).
144 Zhao, W. et al. BRCA1–BARD1 promotes RAD51-mediated homologous DNA pairing. Nature 550, 360-365 (2017).
145 Shiu, J.-L. et al. The HLTF–PARP1 interaction in the progression and stability of damaged replication forks caused by methyl methanesulfonate. Oncogenesis 9, 1-14 (2020).
146 Schärer, O. D. Nucleotide excision repair in eukaryotes. Cold Spring Harbor perspectives in biology 5, a012609 (2013).
147 Petruseva, I. O., Evdokimov, A. N. & Lavrik, O. I. Molecular mechanism of global genome nucleotide excision repair. Acta naturae 6, 23-34 (2014).
148 Masutani, C. et al. Xeroderma pigmentosum variant (XP‐V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity. The EMBO journal 18, 3491-3501 (1999).
149 Masutani, C., Kusumoto, R., Iwai, S. & Hanaoka, F. Mechanisms of accurate translesion synthesis by human DNA polymerase η. The EMBO journal 19, 3100-3109 (2000).
150 McCulloch, S. D. et al. Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity. Nature 428, 97-100 (2004).
151 Vaisman, A., Masutani, C., Hanaoka, F. & Chaney, S. G. Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase η. Biochemistry 39, 4575-4580 (2000).
152 Chaudhuri, A. R. & Nussenzweig, A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nature reviews Molecular cell biology 18, 610-621 (2017).
153 Petermann, E., Orta, M. L., Issaeva, N., Schultz, N. & Helleday, T. Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol Cell 37, 492-502 (2010).
154 Manosas, M., Perumal, S. K., Croquette, V. & Benkovic, S. J. Direct observation of stalled fork restart via fork regression in the T4 replication system. Science 338, 1217-1220 (2012).
155 Wit, N. et al. Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage. Nucleic acids research 43, 282-294 (2015).
156 Edmunds, C. E., Simpson, L. J. & Sale, J. E. PCNA ubiquitination and REV1 define temporally distinct mechanisms for controlling translesion synthesis in the avian cell line DT40. Mol Cell 30, 519-529 (2008).

校內：2026-08-12公開
校外：2026-08-12公開電子論文尚未授權公開，紙本請查館藏目錄

簡易檢索 / 詳目顯示

相關論文