Faculty, Staff and Student Publications
Publication Date
10-1-2023
Journal
Nature Structural & Molecular Biology
Abstract
The extent and efficacy of DNA end resection at DNA double-strand breaks (DSB) determine the repair pathway choice. Here we describe how the 53BP1-associated protein DYNLL1 works in tandem with the Shieldin complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1, where it limits end resection by binding and disrupting the MRE11 dimer. The Shieldin complex is recruited to a fraction of 53BP1-positive DSBs hours after DYNLL1, predominantly in G1 cells. Shieldin localization to DSBs depends on MRE11 activity and is regulated by the interaction of DYNLL1 with MRE11. BRCA1-deficient cells rendered resistant to PARP inhibitors by the loss of Shieldin proteins can be resensitized by the constitutive association of DYNLL1 with MRE11. These results define the temporal and functional dynamics of the 53BP1-centric DNA end resection factors in cells.
Keywords
DNA Breaks, Double-Stranded, BRCA1 Protein, Tumor Suppressor p53-Binding Protein 1, DNA, DNA End-Joining Repair, Cell Nucleus, DNA Repair
DOI
10.1038/s41594-023-01074-9
PMID
37696958
PMCID
PMC10686051
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
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