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PMID: 20064938 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA.

The Journal of biological chemistry ·Vol. 285 ·No. 11 ·2010-03-12 ·Pages 8054-60

Loseva O, Jemth AS, Bryant HE, Schüler H, Lehtiö L, Karlberg T, Helleday T

Abstract

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 ADP-ribose. 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.

MeSH Terms
3-Iodobenzylguanidine/pharmacology Adenosine Diphosphate Ribose/metabolism Camptothecin/pharmacology Cell Cycle Proteins/chemistry,genetics,metabolism DNA/metabolism DNA Breaks, Single-Stranded DNA Repair/physiology DNA Topoisomerases, Type I/metabolism Enzyme Inhibitors/pharmacology Histones/metabolism Humans Hydrolysis Hydroxylamine/pharmacology Mercuric Chloride/pharmacology Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases/chemistry,genetics,metabolism Protein Structure, Tertiary RNA, Small Interfering/metabolism Topoisomerase I Inhibitors
Chemicals
Cell Cycle Proteins Enzyme Inhibitors Histones RNA, Small Interfering Topoisomerase I Inhibitors Adenosine Diphosphate Ribose Hydroxylamine 3-Iodobenzylguanidine Mercuric Chloride DNA PARP1 protein, human PARP3 protein, human Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases DNA Topoisomerases, Type I Camptothecin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Loseva Olga
Department of Genetics, Stockholm University, S-10691 Stockholm, Sweden.
Jemth Ann-Sofie
Bryant Helen E
Schüler Herwig
Lehtiö Lari
Karlberg Tobias
Helleday Thomas
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M109.077834
Published
2010-03-12
Epub
2010-00-11
Pages
8054-60
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2832956
Subset
IM
Grants
Medical Research Council · G0700730 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1074/jbc.M109.077834 PMC Full Text View journal details
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