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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 JeggoKAP-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 BiologyISSN
1545-9993Publisher
Nature Publishing GroupExternal DOI
Issue
7Volume
18Page range
831-839Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-11-01Usage metrics
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