Abro1 maintains genome stability and limits replication stress by protecting replication fork stability

Shengfeng Xu, Xiao Wu, Ling Wu, Andy Castillo, Jianxin Liu, Erin Atkinson, Atanu Paul, Dan Su, Katharina Schlacher, Yoshihiro Komatsu, M. James You, Bin Wang

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Protection of the stalled replication fork is crucial for responding to replication stress and minimizing its impact on chromosome instability, thus preventing diseases, including cancer. We found a new component, Abro1, in the protection of stalled replication fork integrity. Abro1 deficiency results in increased chromosome instability, and Abro1-null mice are tumor-prone. We showthat Abro1 protects stalled replication fork stability by inhibiting DNA2 nuclease/WRN helicase-mediated degradation of stalled forks. Depletion of RAD51 prevents the DNA2/WRN-dependent degradation of stalled forks in Abro1-deficient cells. This mechanism is distinct from the BRCA2-dependent fork protection pathway, in which stable RAD51 filament formation prevents MRE11-dependent degradation of the newly synthesized DNA at stalled forks. Thus, our data reveal a new aspect of regulated protection of stalled replication forks that involves Abro1.

Original languageEnglish (US)
Pages (from-to)1469-1482
Number of pages14
JournalGenes and Development
Volume31
Issue number14
DOIs
StatePublished - 2017

Keywords

  • Abro1
  • BRCA2
  • DNA2
  • MRE11
  • RAD51
  • Stalled replication fork stability

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

MD Anderson CCSG core facilities

  • Functional Genomics Core
  • Research Animal Support Facility

Fingerprint

Dive into the research topics of 'Abro1 maintains genome stability and limits replication stress by protecting replication fork stability'. Together they form a unique fingerprint.

Cite this