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 |
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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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Here, we identify PARP1 separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1. 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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.</description><subject>Biological Sciences</subject><subject>Cell Line, Tumor</subject><subject>Chromatin Assembly and Disassembly</subject><subject>DNA Helicases - metabolism</subject><subject>DNA Repair</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Humans</subject><subject>Nucleosomes - metabolism</subject><subject>Poly (ADP-Ribose) Polymerase-1 - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1v1DAQxS0EokvhzAmUI5e04_j7glit-JK2aoV6txx7UlI5cbATJP77ZrVloacZ6f3mzdMj5C2FCwqKXU6jKxfNujZKUaqfkQ0FQ2vJDTwnG4BG1Zo3_Iy8KuUeAIzQ8JKcMc6lkI3YkE9XS5z7KWKVU8RSdSlXN9sfN7Tqx2q739E64IRjwHGuxsVHTCUNK4xDChj78e41edG5WPDN4zwnt18-3-6-1fvrr993233tORVzLRy0PDhsvUb0DNADkx3nDE1QBpw0zDjOjPHOS40iiBC0bLEVolMg2Dn5eLSdlnbA4Nc82UU75X5w-Y9NrrdPlbH_ae_Sb6s5Y0IfDD48GuT0a8Ey26EvHmN0I6al2EZI3QghFV_RyyPqcyolY3d6Q8EeareH2u2_2teL9_-nO_F_e16Bd0fgvswpn_RGgRKcSvYAptOI8w</recordid><startdate>20210907</startdate><enddate>20210907</enddate><creator>Ooi, Soon-Keat</creator><creator>Sato, Shigeo</creator><creator>Tomomori-Sato, Chieri</creator><creator>Zhang, Ying</creator><creator>Wen, Zhihui</creator><creator>Banks, Charles A. 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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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