RADX Modulates RAD51 Activity to Control Replication Fork Protection

Cell Reports
Kamakoti P BhatDavid Cortez

Abstract

RAD51 promotes homologous recombination repair (HR) of double-strand breaks and acts during DNA replication to facilitate fork reversal and protect nascent DNA strands from nuclease digestion. Several additional HR proteins regulate fork protection by promoting RAD51 filament formation. Here, we show that RADX modulates stalled fork protection by antagonizing RAD51. Consequently, silencing RADX restores fork protection in cells deficient for BRCA1, BRCA2, FANCA, FANCD2, or BOD1L. Inactivating RADX prevents both MRE11- and DNA2-dependent fork degradation. Furthermore, RADX overexpression causes fork degradation that is dependent on these nucleases and fork reversal. The amount of RAD51 determines the fate of stalled replication forks, with more RAD51 required for fork protection than fork reversal. Finally, we find that RADX effectively competes with RAD51 for binding to single-stranded DNA, supporting a model in which RADX buffers RAD51 to ensure the right amount of reversal and protection to maintain genome stability.

Citations

May 24, 2019·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Emily HinchcliffRobert L Coleman
Feb 14, 2020·Cancers·Eva MalacariaPietro Pichierri
May 12, 2020·The Journal of Cell Biology·Haohui DuanShailja Pathania
Sep 29, 2019·Nature Communications·Jennifer M MasonDouglas K Bishop
Dec 6, 2018·Biochemical Society Transactions·Darshil R Patel, Robert S Weiss
Mar 31, 2019·Nature Communications·Eva MalacariaPietro Pichierri
Jan 24, 2019·The Journal of Cell Biology·Kimberly Rickman, Agata Smogorzewska
Jul 5, 2019·Nature·Manuel Daza-MartinJoanna R Morris
Aug 25, 2020·Science Advances·L G BennettC J Staples
Jul 3, 2020·Nature Reviews. Molecular Cell Biology·Matteo BertiMassimo Lopes
Jul 25, 2019·Nature Communications·Chirantani MukherjeeArnab Ray Chaudhuri
Dec 7, 2018·Genes·Félix Prado
Jul 6, 2020·Nucleic Acids Research·Hongshan ZhangIlya J Finkelstein
Jan 17, 2021·Molecular Cell·Madison B AdolphDavid Cortez
Jan 28, 2021·Cell Reports·Arik TownsendHuzefa Dungrawala
Jul 13, 2020·Seminars in Cell & Developmental Biology·Stephanie TyeJoanna R Morris
Oct 31, 2020·Experimental & Molecular Medicine·Fei ZhaoZhenkun Lou
Feb 1, 2020·Pharmacology & Therapeutics·Erik LauriniSabrina Pricl
Nov 14, 2020·Cancer Research·Nicholas J PanzarinoSharon B Cantor
Sep 17, 2020·Science Advances·L G BennettC J Staples
Nov 19, 2020·Trends in Cancer·Katherine E Baillie, Peter C Stirling
May 1, 2021·International Journal of Molecular Sciences·Jessica J R Hudson, Ulrich Rass
May 13, 2021·Nucleic Acids Research·Tanay Thakar, George-Lucian Moldovan
May 11, 2021·Seminars in Cell & Developmental Biology·Christine M KondratickMaria Spies
Jun 10, 2021·Molecular Cell·Archana KrishnamoorthyDavid Cortez
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Hervé Técher, Philippe Pasero
Nov 7, 2021·Nature Communications·Kai-Hang LeiPeter Chi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.