NBS1 Recruits RAD18 via a RAD6-like Domain and Regulates Pol ¦Ç-Dependent Translesion DNA Synthesis

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• 作者：Hiromi Yanagihara¹ ; ¹² ; Junya Kobayashi¹ ; ¹² ; Satoshi Tateishi² ; Akihiro Kato¹ ; Shinya Matsuura³ ; Hiroshi Tauchi⁴ ; Kouichi Yamada⁵ ; Jun Takezawa⁵ ; Kaoru Sugasawa⁶ ; Chikahide Masutani⁷ ; Fumio Hanaoka⁸ ; Corry  ; M. Weemaes⁹ ; Toshio Mori¹⁰ ; Lee Zou¹¹ ; Kenshi Komatsu¹ ; ^{komatsu@house.rbc.kyoto-u.ac.jp}
• 刊名：Molecular Cell
• 出版年：2011
• 出版时间：2 September, 2011
• 年：2011
• 卷：43
• 期：5
• 页码：788-797
• 全文大小：1K

文摘

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Summary

Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Pol¦Ç focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Pol¦Ç-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.