Abro1 Maintains Genome Stability and Limits Replication Stress by Protecting Replication Fork Stability

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2017 Sep 2

PMID 28860160

Citations 41

Authors

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

Affiliations

Soon will be listed here.

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 show that 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.

Citing Articles

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