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, L. Haracska, Stephen J. Elledge

Research output: Contribution to journalArticle

137 Citations (Scopus)

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 languageEnglish
Pages (from-to)396-409
Number of pages14
JournalMolecular Cell
Volume47
Issue number3
DOIs
Publication statusPublished - Aug 10 2012

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Proliferating Cell Nuclear Antigen
Genetic Recombination
DNA
Sister Chromatid Exchange
Genomic Instability
DNA-Directed DNA Polymerase
DNA Replication
DNA Damage
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Ciccia, A., Nimonkar, A. V., Hu, Y., Hajdu, I., Achar, Y. J., Izhar, 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

Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress. / Ciccia, Alberto; Nimonkar, Amitabh V.; Hu, Yiduo; Hajdu, Ildiko; Achar, Yathish Jagadheesh; Izhar, Lior; Petit, Sarah A.; Adamson, Britt; Yoon, John C.; Kowalczykowski, Stephen C.; Livingston, David M.; Haracska, L.; Elledge, Stephen J.

In: Molecular Cell, Vol. 47, No. 3, 10.08.2012, p. 396-409.

Research output: Contribution to journalArticle

Ciccia, A, Nimonkar, AV, Hu, Y, Hajdu, I, Achar, YJ, Izhar, L, Petit, SA, Adamson, B, Yoon, JC, Kowalczykowski, SC, Livingston, DM, Haracska, L & Elledge, SJ 2012, 'Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress', Molecular Cell, vol. 47, no. 3, pp. 396-409. https://doi.org/10.1016/j.molcel.2012.05.024
Ciccia, Alberto ; Nimonkar, Amitabh V. ; Hu, Yiduo ; Hajdu, Ildiko ; Achar, Yathish Jagadheesh ; Izhar, Lior ; Petit, Sarah A. ; Adamson, Britt ; Yoon, John C. ; Kowalczykowski, Stephen C. ; Livingston, David M. ; Haracska, L. ; Elledge, Stephen J. / Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication Stress. In: Molecular Cell. 2012 ; Vol. 47, No. 3. pp. 396-409.
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