Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress

Alberto Ciccia; Amitabh V. Nimonkar; Yiduo Hu; Ildiko Hajdu; Yathish Jagadheesh Achar; Lior Izhar; Sarah A. Petit; Britt Adamson; John C. Yoon; Stephen C. Kowalczykowski; David M. Livingston; Lajos Haracska; Stephen J. Elledge

doi:10.1016/j.molcel.2012.05.024

Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress

Alberto Ciccia, Amitabh V. Nimonkar, Yiduo Hu, Ildiko Hajdu, Yathish Jagadheesh Achar, Lior Izhar, Sarah A. Petit, Britt Adamson, John C. Yoon, Stephen C. Kowalczykowski, David M. Livingston, Lajos Haracska, Stephen J. Elledge

Research output: Contribution to journal › Article › peer-review

229 Scopus citations

Abstract

Completion of DNA replication after replication stress depends on PCNA, which undergoes monoubiquitination to stimulate direct bypass of DNA lesions by specialized DNA polymerases or is polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Here we report that the ZRANB3 translocase, a SNF2 family member related to the SIOD disorder SMARCAL1 protein, is recruited by polyubiquitinated PCNA to promote fork restart following replication arrest. ZRANB3 depletion in mammalian cells results in an increased frequency of sister chromatid exchange and DNA damage sensitivity after treatment with agents that cause replication stress. Using in vitro biochemical assays, we show that recombinant ZRANB3 remodels DNA structures mimicking stalled replication forks and disassembles recombination intermediates. We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events.

Original language	English (US)
Pages (from-to)	396-409
Number of pages	14
Journal	Molecular Cell
Volume	47
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2012.05.024
State	Published - Aug 10 2012
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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Ciccia, A., Nimonkar, A. V., Hu, Y., Hajdu, I., Achar, Y. J., Izhar, L., Petit, S. A., Adamson, B., Yoon, J. C., Kowalczykowski, S. C., Livingston, D. M., Haracska, L., & Elledge, S. J. (2012). Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress. Molecular Cell, 47(3), 396-409. https://doi.org/10.1016/j.molcel.2012.05.024

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title = "Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress",

abstract = "Completion of DNA replication after replication stress depends on PCNA, which undergoes monoubiquitination to stimulate direct bypass of DNA lesions by specialized DNA polymerases or is polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Here we report that the ZRANB3 translocase, a SNF2 family member related to the SIOD disorder SMARCAL1 protein, is recruited by polyubiquitinated PCNA to promote fork restart following replication arrest. ZRANB3 depletion in mammalian cells results in an increased frequency of sister chromatid exchange and DNA damage sensitivity after treatment with agents that cause replication stress. Using in vitro biochemical assays, we show that recombinant ZRANB3 remodels DNA structures mimicking stalled replication forks and disassembles recombination intermediates. We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events.",

author = "Alberto Ciccia and Nimonkar, {Amitabh V.} and Yiduo Hu and Ildiko Hajdu and Achar, {Yathish Jagadheesh} and Lior Izhar and Petit, {Sarah A.} and Britt Adamson and Yoon, {John C.} and Kowalczykowski, {Stephen C.} and Livingston, {David M.} and Lajos Haracska and Elledge, {Stephen J.}",

note = "Funding Information: We thank Andrea Bredemeyer, Artyom Alekseyenko, Satya Prakash, and Jung-Hoon Yoon for help and advice and Alan Lehmann for reagents. A.C. and I.H. are recipients of EMBO long-term fellowships. Y.H. was supported by a U.S. Department of Defense postdoctoral fellowship award (W81XWH-09-1-0632). This work was supported by grants from the National Institute of Health and the National Cancer Institute to S.J.E., D.M.L., J.C.Y., and S.C.K. (grant GM62653) and by Howard Hughes Medical Institute Grant 55005612 and Hungarian Science Foundation Grants OTKA 77495 and TAMOP-4.2.2/08/1 to L.H. S.J.E. is a Howard Hughes Medical Institute investigator. ",

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doi = "10.1016/j.molcel.2012.05.024",

language = "English (US)",

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T1 - Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress

AU - Ciccia, Alberto

AU - Nimonkar, Amitabh V.

AU - Hu, Yiduo

AU - Hajdu, Ildiko

AU - Achar, Yathish Jagadheesh

AU - Izhar, Lior

AU - Petit, Sarah A.

AU - Adamson, Britt

AU - Yoon, John C.

AU - Kowalczykowski, Stephen C.

AU - Livingston, David M.

AU - Haracska, Lajos

AU - Elledge, Stephen J.

N1 - Funding Information: We thank Andrea Bredemeyer, Artyom Alekseyenko, Satya Prakash, and Jung-Hoon Yoon for help and advice and Alan Lehmann for reagents. A.C. and I.H. are recipients of EMBO long-term fellowships. Y.H. was supported by a U.S. Department of Defense postdoctoral fellowship award (W81XWH-09-1-0632). This work was supported by grants from the National Institute of Health and the National Cancer Institute to S.J.E., D.M.L., J.C.Y., and S.C.K. (grant GM62653) and by Howard Hughes Medical Institute Grant 55005612 and Hungarian Science Foundation Grants OTKA 77495 and TAMOP-4.2.2/08/1 to L.H. S.J.E. is a Howard Hughes Medical Institute investigator.

PY - 2012/8/10

Y1 - 2012/8/10

N2 - Completion of DNA replication after replication stress depends on PCNA, which undergoes monoubiquitination to stimulate direct bypass of DNA lesions by specialized DNA polymerases or is polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Here we report that the ZRANB3 translocase, a SNF2 family member related to the SIOD disorder SMARCAL1 protein, is recruited by polyubiquitinated PCNA to promote fork restart following replication arrest. ZRANB3 depletion in mammalian cells results in an increased frequency of sister chromatid exchange and DNA damage sensitivity after treatment with agents that cause replication stress. Using in vitro biochemical assays, we show that recombinant ZRANB3 remodels DNA structures mimicking stalled replication forks and disassembles recombination intermediates. We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events.

AB - Completion of DNA replication after replication stress depends on PCNA, which undergoes monoubiquitination to stimulate direct bypass of DNA lesions by specialized DNA polymerases or is polyubiquitinated to promote recombination-dependent DNA synthesis across DNA lesions by template switching mechanisms. Here we report that the ZRANB3 translocase, a SNF2 family member related to the SIOD disorder SMARCAL1 protein, is recruited by polyubiquitinated PCNA to promote fork restart following replication arrest. ZRANB3 depletion in mammalian cells results in an increased frequency of sister chromatid exchange and DNA damage sensitivity after treatment with agents that cause replication stress. Using in vitro biochemical assays, we show that recombinant ZRANB3 remodels DNA structures mimicking stalled replication forks and disassembles recombination intermediates. We therefore propose that ZRANB3 maintains genomic stability at stalled or collapsed replication forks by facilitating fork restart and limiting inappropriate recombination that could occur during template switching events.

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JF - Molecular Cell

IS - 3

ER -

Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress

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