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KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response

journal contribution
posted on 2023-06-08, 12:36 authored by Aaron A Goodarzi, Thomas Kurka, Penny Jeggo
KAP-1 poses a substantial barrier to DNA double-strand break (DSB) repair within heterochromatin that is alleviated by ATM-dependent KAP-1 phosphorylation (pKAP-1). Here we address the mechanistic consequences of pKAP-1 that promote heterochromatic DSB repair and chromatin relaxation. KAP-1 function involves autoSUMOylation and recruitment of nucleosome deacetylation, methylation and remodeling activities. Although heterochromatin acetylation or methylation changes were not detected, radiation-induced pKAP-1 dispersed the nucleosome remodeler CHD3 from DSBs and triggered concomitant chromatin relaxation; pKAP-1 loss reversed these effects. Depletion or inactivation of CHD3, or ablation of its interaction with KAP-1(SUMO1), bypassed pKAP-1's role in repair. Though KAP-1 SUMOylation was unaffected after irradiation, CHD3 dissociated from KAP-1(SUMO1) in a pKAP-1-dependent manner. We demonstrate that KAP-1(Ser824) phosphorylation generates a motif that directly perturbs interactions between CHD3's SUMO-interacting motif and SUMO1, dispersing CHD3 from heterochromatin DSBs and enabling repair.

History

Publication status

  • Published

Journal

Nature Structural and Molecular Biology

ISSN

1545-9993

Publisher

Nature Publishing Group

Issue

7

Volume

18

Page range

831-839

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-11-01

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