TY - JOUR
T1 - BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade
AU - Tian, Fen
AU - Sharma, Shilpy
AU - Zou, Jianqiu
AU - Lin, Shiaw Yih
AU - Wang, Bin
AU - Rezvani, Khosrow
AU - Wang, Hongmin
AU - Parvin, Jeffrey D.
AU - Ludwig, Thomas
AU - Canman, Christine E.
AU - Zhang, Dong
PY - 2013/8/13
Y1 - 2013/8/13
N2 - Breast cancer gene 1 (BRCA1) deficient cells not only are hypersensitive to double-strand breaks but also are hypersensitive to UV irradiation and other agents that cause replication blockade; however, the molecular mechanisms behind these latter sensitivities are largely unknown. Here, we report that BRCA1 promotes cell survival by directly regulating the DNA damage tolerance pathway in response to agents that create cross-links in DNA. We show that BRCA1 not only promotes efficient mono-and polyubiquitination of proliferating cell nuclear antigen (PCNA) by regulating the recruitment of replication protein A, Rad18, and helicase-like transcription factor to chromatin but also directly recruits translesion polymerases, such as Polymerase eta and Rev1, to the lesions through protein-protein interactions. Our data suggest that BRCA1 plays a critical role in promoting translesion DNA synthesis as well as DNA template switching.
AB - Breast cancer gene 1 (BRCA1) deficient cells not only are hypersensitive to double-strand breaks but also are hypersensitive to UV irradiation and other agents that cause replication blockade; however, the molecular mechanisms behind these latter sensitivities are largely unknown. Here, we report that BRCA1 promotes cell survival by directly regulating the DNA damage tolerance pathway in response to agents that create cross-links in DNA. We show that BRCA1 not only promotes efficient mono-and polyubiquitination of proliferating cell nuclear antigen (PCNA) by regulating the recruitment of replication protein A, Rad18, and helicase-like transcription factor to chromatin but also directly recruits translesion polymerases, such as Polymerase eta and Rev1, to the lesions through protein-protein interactions. Our data suggest that BRCA1 plays a critical role in promoting translesion DNA synthesis as well as DNA template switching.
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U2 - 10.1073/pnas.1306534110
DO - 10.1073/pnas.1306534110
M3 - Article
C2 - 23901102
AN - SCOPUS:84882402547
SN - 0027-8424
VL - 110
SP - 13558
EP - 13563
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -
