TY - JOUR
T1 - Opposing ISWI- and CHD-class chromatin remodeling activities orchestrate heterochromatic DNA repair
AU - Klement, Karolin
AU - Luijsterburg, Martijn S.
AU - Pinder, Jordan B.
AU - Cena, Chad S.
AU - Del Nero, Victor
AU - Wintersinger, Christopher M.
AU - Dellaire, Graham
AU - van Attikum, Haico
AU - Goodarzi, Aaron A.
N1 - Publisher Copyright:
© 2014 Klement et al.
PY - 2014
Y1 - 2014
N2 - Heterochromatin is a barrier to DNA repair that correlates strongly with elevated somatic mutation in cancer. CHD class II nucleosome remodeling activity (specifically CHD3.1) retained by KAP-1 increases heterochromatin compaction and impedes DNA doublestrand break (DSB) repair requiring Artemis. This obstruction is alleviated by chromatin relaxation via ATMdependent KAP-1S824 phosphorylation (pKAP-1) and CHD3.1 dispersal from heterochromatic DSBs; however, how heterochromatin compaction is actually adjusted after CHD3.1 dispersal is unknown. In this paper, we demonstrate that Artemis-dependent DSB repair in heterochromatin requires ISWI (imitation switch)-class ACF1-SNF2H nucleosome remodeling. Compacted chromatin generated by CHD3.1 after DNA replication necessitates ACF1-SNF2H- mediated relaxation for DSB repair. ACF1-SNF2H requires RNF20 to bind heterochromatic DSBs, underlies RNF20- mediated chromatin relaxation, and functions downstream of pKAP-1-mediated CHD3.1 dispersal to enable DSB repair. CHD3.1 and ACF1-SNF2H display counteractive activities but similar histone affinities (via the plant homeodomains of CHD3.1 and ACF1), which we suggest necessitates a two-step dispersal and recruitment system regulating these opposing chromatin remodeling activities during DSB repair.
AB - Heterochromatin is a barrier to DNA repair that correlates strongly with elevated somatic mutation in cancer. CHD class II nucleosome remodeling activity (specifically CHD3.1) retained by KAP-1 increases heterochromatin compaction and impedes DNA doublestrand break (DSB) repair requiring Artemis. This obstruction is alleviated by chromatin relaxation via ATMdependent KAP-1S824 phosphorylation (pKAP-1) and CHD3.1 dispersal from heterochromatic DSBs; however, how heterochromatin compaction is actually adjusted after CHD3.1 dispersal is unknown. In this paper, we demonstrate that Artemis-dependent DSB repair in heterochromatin requires ISWI (imitation switch)-class ACF1-SNF2H nucleosome remodeling. Compacted chromatin generated by CHD3.1 after DNA replication necessitates ACF1-SNF2H- mediated relaxation for DSB repair. ACF1-SNF2H requires RNF20 to bind heterochromatic DSBs, underlies RNF20- mediated chromatin relaxation, and functions downstream of pKAP-1-mediated CHD3.1 dispersal to enable DSB repair. CHD3.1 and ACF1-SNF2H display counteractive activities but similar histone affinities (via the plant homeodomains of CHD3.1 and ACF1), which we suggest necessitates a two-step dispersal and recruitment system regulating these opposing chromatin remodeling activities during DSB repair.
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U2 - 10.1083/jcb.201405077
DO - 10.1083/jcb.201405077
M3 - Article
C2 - 25533843
AN - SCOPUS:84930469938
SN - 0021-9525
VL - 207
SP - 717
EP - 733
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -
