PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA.
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.
Loseva
Olga
O
Department of Genetics, Stockholm University, S-10691 Stockholm, Sweden.
Jemth
Ann-Sofie
AS
Bryant
Helen E
HE
Schüler
Herwig
H
Lehtiö
Lari
L
Karlberg
Tobias
T
Helleday
Thomas
T
D019797:3-Iodobenzylguanidine / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D002166:Camptothecin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000502:physiology*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D019811:Hydroxylamine / Q000494:pharmacology; D008627:Mercuric Chloride / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D059004:Topoisomerase I Inhibitors
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D034741:RNA, Small Interfering; D059004:Topoisomerase I Inhibitors; D000246:Adenosine Diphosphate Ribose; D019811:Hydroxylamine; D019797:3-Iodobenzylguanidine; D008627:Mercuric Chloride; D004247:DNA; C499320:PARP1 protein, human; C480979:PARP3 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin