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WRNIP 1 protects stalled forks from degradation and promotes fork restart after replication stress
Author(s) -
Leuzzi Giuseppe,
Marabitti Veronica,
Pichierri Pietro,
Franchitto Annapaola
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201593265
Subject(s) - biology , fork (system call) , replication (statistics) , degradation (telecommunications) , microbiology and biotechnology , genetics , virology , computer science , operating system , telecommunications
Accurate handling of stalled replication forks is crucial for the maintenance of genome stability. RAD 51 defends stalled replication forks from nucleolytic attack, which otherwise can threaten genome stability. However, the identity of other factors that can collaborate with RAD 51 in this task is poorly elucidated. Here, we establish that human Werner helicase interacting protein 1 ( WRNIP 1) is localized to stalled replication forks and cooperates with RAD 51 to safeguard fork integrity. We show that WRNIP 1 is directly involved in preventing uncontrolled MRE 11‐mediated degradation of stalled replication forks by promoting RAD 51 stabilization on ss DNA . We further demonstrate that replication fork protection does not require the ATP ase activity of WRNIP 1 that is however essential to achieve the recovery of perturbed replication forks. Loss of WRNIP 1 or its catalytic activity causes extensive DNA damage and chromosomal aberrations. Intriguingly, downregulation of the anti‐recombinase FBH 1 can compensate for loss of WRNIP 1 activity, since it attenuates replication fork degradation and chromosomal aberrations in WRNIP 1‐deficient cells. Therefore, these findings unveil a unique role for WRNIP 1 as a replication fork‐protective factor in maintaining genome stability.