Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling.

Ooi, Soon-Keat; Sato, Shigeo; Tomomori-Sato, Chieri; Zhang, Ying; Wen, Zhihui; Banks, Charles A S; Washburn, Michael P; Unruh, Jay R et al. · Proc Natl Acad Sci U S A · 2021

basic_science · Level V

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Abstract

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<sup>+</sup> 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.

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