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RADX Promotes Genome Stability and Modulates Chemosensitivity by Regulating RAD51 at Replication Forks.

  1. Author:
    Dungrawala, Huzefa
    Bhat, Kamakoti P
    Le Meur, Rémy
    Chazin, Walter J
    Ding, Xia
    Sharan, Shyam
    Wessel, Sarah R
    Sathe, Aditya A
    Zhao, Runxiang
    Cortez, David

  2. Author Address

    Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA., Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN, USA., Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA., Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: david.cortez@vanderbilt.edu.,
    1. Year: 2017
    2. Date: Aug 3
    3. Epub Date: 2017 Jul 19
  2. Journal: Molecular cell
    1. 67
    2. 3
    3. Pages: 374-+
  4. Type of Article: Article
  5. ISSN: 1097-2765
  1. Abstract:

    RAD51 promotes homology-directed repair (HDR), replication fork reversal, and stalled fork protection. Defects in these functions cause genomic instability and tumorigenesis but also generate hypersensitivity to cancer therapeutics. Here we describe the identification of RADX as an RPA-like, single-strand DNA binding protein. RADX is recruited to replication forks, where it prevents fork collapse by regulating RAD51. When RADX is inactivated, excessive RAD51 activity slows replication elongation and causes double-strand breaks. In cancer cells lacking BRCA2, RADX deletion restores fork protection without restoring HDR. Furthermore, RADX inactivation confers chemotherapy and PARP inhibitor resistance to cancer cells with reduced BRCA2/RAD51 pathway function. By antagonizing RAD51 at forks, RADX allows cells to maintain a high capacity for HDR while ensuring that replication functions of RAD51 are properly regulated. Thus, RADX is essential to achieve the proper balance of RAD51 activity to maintain genome stability. Copyright © 2017 Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.molcel.2017.06.023
  3. PMID: 28735897
  4. View record in Web of Science®
  5. WOS: 000406861800004

Library Notes

  1. Fiscal Year: FY2016-2017
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