Activation of the SNF2 family ATPase ALC1 by poly(ADP-ribose) in a stable ALC1·PARP1·nucleosome intermediate

Aaron J. Gottschalk, Rushi D. Trivedi, Joan W. Conaway, Ronald C. Conaway

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The human ALC1/CHD1L oncogene encodes an SNF2 family ATPase with a macrodomain that binds poly(ADP-ribose) (PAR). We and others previously showed that ALC1 possesses a cryptic ATP-dependent nucleosome remodeling activity that is potently activated in the presence of PARP1 and NAD+, its substrate for PAR synthesis. In this work, we dissected the mechanism by which PARP1 and NAD+ activate ALC1 nucleosome remodeling. We demonstrate that ALC1 activation depends on the formation of a stable ALC1·PARylated PARP1·nucleosome intermediate. In addition, by exploiting a novel PAR footprinting assay, we obtained evidence that the ALC1 macrodomain remains stably associated with PAR on auto PARylated PARP1 during the course of nucleosome remodeling reactions. Taken together, our findings are consistent with the model that PAR present on PARylated PARP1 acts as an allosteric effector of ALC1 nucleosome remodeling activity.

Original languageEnglish (US)
Pages (from-to)43527-43532
Number of pages6
JournalJournal of Biological Chemistry
Volume287
Issue number52
DOIs
StatePublished - Dec 21 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Activation of the SNF2 family ATPase ALC1 by poly(ADP-ribose) in a stable ALC1·PARP1·nucleosome intermediate'. Together they form a unique fingerprint.

Cite this