Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity

Molecular Cell
Molly C KottemannAgata Smogorzewska

Abstract

The protection and efficient restart of stalled replication forks is critical for the maintenance of genome integrity. Here, we identify a regulatory pathway that promotes stalled forks recovery from replication stress. We show that the mammalian replisome component C20orf43/RTF2 (homologous to S. pombe Rtf2) must be removed for fork restart to be optimal. We further show that the proteasomal shuttle proteins DDI1 and DDI2 are required for RTF2 removal from stalled forks. Persistence of RTF2 at stalled forks results in fork restart defects, hyperactivation of the DNA damage signal, accumulation of single-stranded DNA (ssDNA), sensitivity to replication drugs, and chromosome instability. These results establish that RTF2 removal is a key determinant for the ability of cells to manage replication stress and maintain genome integrity.

Citations

May 28, 2019·Apoptosis : an International Journal on Programmed Cell Death·Lei LeiJin Yang
May 19, 2020·Human Molecular Genetics·Arun Mouli KolinjivadiJoanne Ngeow
Aug 19, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Heng ZhangQun Liu
Jan 18, 2020·International Journal of Molecular Sciences·Amy NorthropSenthil K Radhakrishnan
Jul 22, 2019·DNA Repair·Julie RageulHyungjin Kim
Jan 8, 2021·Frontiers in Cell and Developmental Biology·Manideep C PachvaRegina Groisman
Jan 6, 2021·Communications Biology·Annamaria Ruggiano, Kristijan Ramadan
Jan 7, 2020·Molecular Cell·Nataliia SerbynFrançoise Stutz
Feb 23, 2021·Trends in Cell Biology·Ann Schirin MirsanayeNiels Mailand

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