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

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

Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2018
Autor(en): Juhász, Szilvia ; Elbakry, Amira ; Mathes, Arthur ; Löbrich, Markus
Titel: ATRX Promotes DNA Repair Synthesis and Sister Chromatid Exchange during Homologous Recombination.
Sprache: Englisch
Kurzbeschreibung (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.

Titel der Zeitschrift, Zeitung oder Schriftenreihe: Molecular cell
Band: 71
(Heft-)Nummer: 1
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Radiation Biology and DNA Repair
Hinterlegungsdatum: 03 Jul 2018 10:44
ID-Nummer: pmid:29937341
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