PARP-3 Is a Mono-ADP-ribosylase That Activates PARP-1 in the Absence of DNA
2010 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 285, no 11, 8054-8060 p.Article in journal (Refereed) Published
The PARP-3 protein is closely related to the PARP-1 and PARP-2 proteins, which are involved in DNA repair and genome maintenance. Here, we characterized the biochemical properties of human PARP-3. PARP-3 is able to ADP-ribosylate itself as well as histone H1, a previously unknown substrate for PARP-3. PARP-3 is not activated upon binding to DNA and is a mono-ADP-ribosylase, in contrast to PARP-1 and PARP-2. PARP-3 interacts with PARP-1 and activates PARP-1 in the absence of DNA, resulting in synthesis of polymers of ADPribose. The N-terminal WGR domain of PARP-3 is involved in this activation. The functional interaction between PARP-3 and PARP-1 suggests that it may have a role in DNA repair. However, here we report that PARP-3 small interfering RNA-depleted cells are not sensitive to the topoisomerase I poison camptothecin, inducing DNA single-strand breaks, and repair these lesions as efficiently as wild-type cells. Altogether, these results suggest that the interaction between PARP-1 and PARP-3 is unrelated to DNA single-strand break repair.
Place, publisher, year, edition, pages
2010. Vol. 285, no 11, 8054-8060 p.
IdentifiersURN: urn:nbn:se:su:diva-50504DOI: 10.1074/jbc.M109.077834ISI: 000275413800023OAI: oai:DiVA.org:su-50504DiVA: diva2:383543
authorCount :72011-01-052010-12-282011-01-05Bibliographically approved