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ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination.

Juhász, Szilvia and Elbakry, Amira and Mathes, Arthur and Löbrich, Markus :
ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination.
In: Molecular cell, 71 (1) p. 11. ISSN 1097-4164
[Article] , (2018)

Abstract

ATRX is a chromatin remodeler that, together with its chaperone DAXX, deposits the histone variant H3.3 in pericentromeric and telomeric regions. Notably, ATRX is frequently mutated in tumors that maintain telomere length by a specific form of homologous recombination (HR). Surprisingly, in this context, we demonstrate that ATRX-deficient cells exhibit a defect in repairing exogenously induced DNA double-strand breaks (DSBs) by HR. ATRX operates downstream of the Rad51 removal step and interacts with PCNA and RFC-1, which are collectively required for DNA repair synthesis during HR. ATRX depletion abolishes DNA repair synthesis and prevents the formation of sister chromatid exchanges at exogenously induced DSBs. DAXX- and H3.3-depleted cells exhibit identical HR defects as ATRX-depleted cells, and both ATRX and DAXX function to deposit H3.3 during DNA repair synthesis. This suggests that ATRX facilitates the chromatin reconstitution required for extended DNA repair synthesis and sister chromatid exchange during HR.

Item Type: Article
Erschienen: 2018
Creators: Juhász, Szilvia and Elbakry, Amira and Mathes, Arthur and Löbrich, Markus
Title: ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination.
Language: English
Abstract:

ATRX is a chromatin remodeler that, together with its chaperone DAXX, deposits the histone variant H3.3 in pericentromeric and telomeric regions. Notably, ATRX is frequently mutated in tumors that maintain telomere length by a specific form of homologous recombination (HR). Surprisingly, in this context, we demonstrate that ATRX-deficient cells exhibit a defect in repairing exogenously induced DNA double-strand breaks (DSBs) by HR. ATRX operates downstream of the Rad51 removal step and interacts with PCNA and RFC-1, which are collectively required for DNA repair synthesis during HR. ATRX depletion abolishes DNA repair synthesis and prevents the formation of sister chromatid exchanges at exogenously induced DSBs. DAXX- and H3.3-depleted cells exhibit identical HR defects as ATRX-depleted cells, and both ATRX and DAXX function to deposit H3.3 during DNA repair synthesis. This suggests that ATRX facilitates the chromatin reconstitution required for extended DNA repair synthesis and sister chromatid exchange during HR.

Journal or Publication Title: Molecular cell
Volume: 71
Number: 1
Divisions: 10 Department of Biology
10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 03 Jul 2018 10:44
Identification Number: pmid:29937341
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