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ATM Release at Resected Double-Strand Breaks Provides Heterochromatin Reconstitution to Facilitate Homologous Recombination

Geuting, Verena ; Reul, Christian ; Löbrich, Markus (2021):
ATM Release at Resected Double-Strand Breaks Provides Heterochromatin Reconstitution to Facilitate Homologous Recombination. (Publisher's Version)
In: PLOS Genetics, 9 (8), PLOS, ISSN 1553-7390, e-ISSN 1553-7404,
DOI: 10.26083/tuprints-00019033,
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Item Type: Article
Origin: Secondary publication service
Status: Publisher's Version
Title: ATM Release at Resected Double-Strand Breaks Provides Heterochromatin Reconstitution to Facilitate Homologous Recombination
Language: English
Abstract:

Non-homologous end-joining (NHEJ) and homologous recombination (HR) represent the two main pathways for repairing DNA double-strand breaks (DSBs). During the G2 phase of the mammalian cell cycle, both processes can operate and chromatin structure is one important factor which determines DSB repair pathway choice. ATM facilitates the repair of heterochromatic DSBs by phosphorylating and inactivating the heterochromatin building factor KAP-1, leading to local chromatin relaxation. Here, we show that ATM accumulation and activity is strongly diminished at DSBs undergoing end-resection during HR. Such DSBs remain unrepaired in cells devoid of the HR factors BRCA2, XRCC3 or RAD51. Strikingly, depletion of KAP-1 or expression of phospho-mimic KAP-1 allows repair of resected DSBs in the absence of BRCA2, XRCC3 or RAD51 by an erroneous PARP-dependent alt-NHEJ process. We suggest that DSBs in heterochromatin elicit initial local heterochromatin relaxation which is reversed during HR due to the release of ATM from resection break ends. The restored heterochromatic structure facilitates HR and prevents usage of error-prone alternative processes.

Journal or Publication Title: PLOS Genetics
Journal volume: 9
Number: 8
Publisher: PLOS
Collation: 14 Seiten
Classification DDC: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Divisions: 10 Department of Biology > Radiation Biology and DNA Repair
Date Deposited: 18 Aug 2021 12:05
Last Modified: 18 Aug 2021 12:05
DOI: 10.26083/tuprints-00019033
Corresponding Links:
URN: urn:nbn:de:tuda-tuprints-190332
URI: https://tuprints.ulb.tu-darmstadt.de/id/eprint/19033
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