ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress
Cited 0 times inCited 0 times in
- ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress
- Park, Su Hyung; Kang, Nalae; Song, Eunho; Wie, Minwoo; Lee, Eun A.; Hwang, Sunyoung; Lee, Deokjae; Ra, Jae Sun; Park, In Bae; Park, Jieun; Kang, Sukhyun; Park, Jun Hong; Hohng, Sungchul; Lee, Kyoo-young; Myung, Kyungjae
- Issue Date
- Nature Publishing Group
- NATURE COMMUNICATIONS, v.10, no.1, pp.5718
- Maintaining stability of replication forks is important for genomic integrity. However, it is not clear how replisome proteins contribute to fork stability under replication stress. Here, we report that ATAD5, a PCNA unloader, plays multiple functions at stalled forks including promoting its restart. ATAD5 depletion increases genomic instability upon hydroxyurea treatment in cultured cells and mice. ATAD5 recruits RAD51 to stalled forks in an ATR kinase-dependent manner by hydroxyurea-enhanced protein-protein interactions and timely removes PCNA from stalled forks for RAD51 recruitment. Consistent with the role of RAD51 in fork regression, ATAD5 depletion inhibits slowdown of fork progression and native 5-bromo-2ʹ-deoxyuridine signal induced by hydroxyurea. Single-molecule FRET showed that PCNA itself acts as a mechanical barrier to fork regression. Consequently, DNA breaks required for fork restart are reduced by ATAD5 depletion. Collectively, our results suggest an important role of ATAD5 in maintaining genome integrity during replication stress.
- Appears in Collections:
- SLS_Journal Papers
- Files in This Item:
Nat. Comm._2019_ATAD5 promotes replication restart by regulating RAD51 and PCNA in response to replication stress.pdf
can give you direct access to the published full text of this article. (UNISTARs only)
Show full item record
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.