Restriction of replication fork regression activities by a conserved SMC complex

Xiaoyu Xue, Koyi Choi, Jaclyn Bonner, Tamara Chiba, Youngho Kwon, Yuanyuan Xu, Humberto Sanchez, Claire Wyman, Hengyao Niu, Xiaolan Zhao, Patrick Sung

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Conserved, multitasking DNA helicases mediate diverse DNA transactions and are relevant for human disease pathogenesis. These helicases and their regulation help maintain genome stability during DNA replication and repair. We show that the structural maintenance of chromosome complex Smc5-Smc6 restrains the replication fork regression activity of Mph1 helicase, but not its D loop disruptive activity. This regulatory mechanism enables flexibility in replication fork repair without interfering with DNA break repair. Invitro studies find that Smc5-Smc6 binds to a Mph1 region required for efficient fork regression, preventing assembly of Mph1 oligomers at the junction of DNA forks. Invivo impairment of this regulatorymechanism compensates for the inactivation of another fork regression helicase and increases reliance on joint DNA structure removal or avoidance. Our findings provide molecular insights into replication fork repair regulation and uncover a role of Smc5-Smc6 in directing Mph1 activity toward a specific biochemical outcome.

Original languageEnglish (US)
Pages (from-to)436-445
Number of pages10
JournalMolecular Cell
Volume56
Issue number3
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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