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XRCC2 Regulates Replication Fork Progression during dNTP Alterations

Saxena, Sneha and Somyajit, Kumar and Nagaraju, Ganesh (2018) XRCC2 Regulates Replication Fork Progression during dNTP Alterations. In: CELL REPORTS, 25 (12). 3273+.

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Official URL: http://dx.doi.org/10.1016/j.celrep.2018.11.085

Abstract

RAD51 paralogs are essential for maintenance of genomic integrity through protection of stalled replication forks and homology-directed repair (HDR) of double-strand breaks. Here, we find that a subset of RAD51 paralogs, XRCC2 (FANCU) and its binding partner RAD51D, restrain active DNA synthesis during dinucleotide triphosphate (dNTP) alterations in a manner independent of HDR. The absence of XRCC2 is associated with increased levels of RRM2, the regulatory subunit of ribonucleotide reductase (RNR), and concomitantly high nucleotide pools, leading to unrestrained fork progression and accumulation of DNA damage during dNTP alterations. Mechanistically, this function is independent of redox signaling and RAD51-mediated fork reversal and is regulated by ataxia-telangiectasia and Rad3-related (ATR) signaling through phosphorylation of XRCC2 (Ser247). Together, these findings identify roles of RAD51 paralogs in the control of replication fork progression and maintenance of genome stability during nucleotide pool alterations.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to CELL PRESS
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Id for Latest eprints
Date Deposited: 28 Jan 2019 05:46
Last Modified: 28 Jan 2019 05:46
URI: http://eprints.iisc.ac.in/id/eprint/61442

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