Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling

The SNF2 family ATPase Amplified in Liver Cancer 1 (ALC1) is the only chromatin remodeling enzyme with a poly(ADP-ribose) (PAR) binding macrodomain. ALC1 functions together with poly(ADP-ribose) polymerase PARP1 to remodel nucleosomes. Activation of ALC1 cryptic ATPase activity and the subsequent nu...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2021-09, Vol.118 (36), p.1-7
Hauptverfasser: Ooi, Soon-Keat, Sato, Shigeo, Tomomori-Sato, Chieri, Zhang, Ying, Wen, Zhihui, Banks, Charles A. S., Washburn, Michael P., Unruh, Jay R., Florens, Laurence, Conaway, Ronald C., Conaway, Joan W.
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container_issue 36
container_start_page 1
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 118
creator Ooi, Soon-Keat
Sato, Shigeo
Tomomori-Sato, Chieri
Zhang, Ying
Wen, Zhihui
Banks, Charles A. S.
Washburn, Michael P.
Unruh, Jay R.
Florens, Laurence
Conaway, Ronald C.
Conaway, Joan W.
description The SNF2 family ATPase Amplified in Liver Cancer 1 (ALC1) is the only chromatin remodeling enzyme with a poly(ADP-ribose) (PAR) binding macrodomain. ALC1 functions together with poly(ADP-ribose) polymerase PARP1 to remodel nucleosomes. Activation of ALC1 cryptic ATPase activity and the subsequent nucleosome remodeling requires binding of its macrodomain to PAR chains synthesized by PARP1 and NAD⁺. A key question is whether PARP1 has a role(s) in ALC1-dependent nucleosome remodeling beyond simply synthesizing the PAR chains needed to activate the ALC1 ATPase. Here, we identify PARP1 separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1. Investigation of these mutants has revealed multiple functions for PARP1 in ALC1-dependent nucleosome remodeling and provides insights into its multifaceted role in chromatin remodeling.
doi_str_mv 10.1073/pnas.2107277118
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subjects Biological Sciences
Cell Line, Tumor
Chromatin Assembly and Disassembly
DNA Helicases - metabolism
DNA Repair
DNA-Binding Proteins - metabolism
Humans
Nucleosomes - metabolism
Poly (ADP-Ribose) Polymerase-1 - metabolism
title Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling
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