BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade

Fen Tian, Shilpy Sharma, Jianqiu Zou, Shiaw Yih Lin, Bin Wang, Khosrow Rezvani, Hongmin Wang, Jeffrey D. Parvin, Thomas Ludwig, Christine E. Canman, Dong Zhang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13558-13563
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number33
DOIs
StatePublished - Aug 13 2013
Externally publishedYes

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Neoplasm Genes
Ubiquitination
Proliferating Cell Nuclear Antigen
Breast Neoplasms
DNA
Replication Protein A
DNA Damage
Chromatin
Cell Survival
Proteins
Transcription Factors

ASJC Scopus subject areas

  • General

Cite this

BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade. / Tian, Fen; Sharma, Shilpy; Zou, Jianqiu; Lin, Shiaw Yih; Wang, Bin; Rezvani, Khosrow; Wang, Hongmin; Parvin, Jeffrey D.; Ludwig, Thomas; Canman, Christine E.; Zhang, Dong.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 33, 13.08.2013, p. 13558-13563.

Research output: Contribution to journalArticle

Tian, Fen ; Sharma, Shilpy ; Zou, Jianqiu ; Lin, Shiaw Yih ; Wang, Bin ; Rezvani, Khosrow ; Wang, Hongmin ; Parvin, Jeffrey D. ; Ludwig, Thomas ; Canman, Christine E. ; Zhang, Dong. / BRCA1 promotes the ubiquitination of PCNA and recruitment of translesion polymerases in response to replication blockade. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 33. pp. 13558-13563.
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abstract = "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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AU - Wang, Bin

AU - Rezvani, Khosrow

AU - Wang, Hongmin

AU - Parvin, Jeffrey D.

AU - Ludwig, Thomas

AU - Canman, Christine E.

AU - Zhang, Dong

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