Abstract
ALC1 is a macrodomain‐containing SNF2‐family ATPase with apparent roles in DNA repair and transcription and has been implicated in the pathogenesis of various cancers. ALC1 displays robust catalytic activity only when its macrodomain interacts with the poly(ADP‐ribose) (PAR) on nucleosome‐bound PARP‐1. However, little is known about the mechanism by which PARylated PARP‐1 regulates ALC1 activity. We seek to define the features of PARP‐1 required for ALC1 activation. PARP‐1 is a multi‐domain enzyme that catalyzes most PAR synthesis in cells. PARP‐1 includes DNA‐binding zinc finger domains (Zn1, Zn2 and Zn3), BRCA1 C‐terminal domain (BRCT), tryptophan‐glycine‐arginine‐rich domain (WGR) and catalytic domain (CAT). As studies have found that Zn2 and BRCT domains are dispensable for PARP‐1's PARylation activity, we have tested PARP‐1 mutants lacking certain domains for their abilities to activate ALC1. Our results thus far show that Zn2 and BRCT domains of PARP‐1 are also dispensable for ALC1 nucleosome remodeling activity.
Published Version
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