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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3-Iodobenzylguanidine / pharmacology
-
Adenosine Diphosphate Ribose / metabolism*
-
Camptothecin / pharmacology
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / 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
-
Poly(ADP-ribose) Polymerases / genetics
-
Poly(ADP-ribose) Polymerases / metabolism*
-
Protein Structure, Tertiary
-
RNA, Small Interfering / metabolism
-
Topoisomerase I Inhibitors
Substances
-
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