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

Loseva, Olga ; Jemth, Ann-Sofie ; Bryant, Helen E ; Schüler, Herwig LU orcid ; Lehtiö, Lari ; Karlberg, Tobias LU and Helleday, Thomas (2010) In The Journal of biological chemistry 285(11). p.60-8054
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... (More)

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.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
3-Iodobenzylguanidine/pharmacology, Adenosine Diphosphate Ribose/metabolism, Camptothecin/pharmacology, Cell Cycle Proteins/chemistry, 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, Protein Structure, Tertiary, RNA, Small Interfering/metabolism, Topoisomerase I Inhibitors
in
The Journal of biological chemistry
volume
285
issue
11
pages
7 pages
publisher
American Society for Biochemistry and Molecular Biology
external identifiers
  • pmid:20064938
  • scopus:77950915348
ISSN
1083-351X
DOI
10.1074/jbc.M109.077834
language
English
LU publication?
no
id
964ab366-cf3a-4fe6-85b0-0c6136bee1ec
date added to LUP
2024-11-21 18:02:20
date last changed
2025-07-19 00:28:32
@article{964ab366-cf3a-4fe6-85b0-0c6136bee1ec,
  abstract     = {{<p>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.</p>}},
  author       = {{Loseva, Olga and Jemth, Ann-Sofie and Bryant, Helen E and Schüler, Herwig and Lehtiö, Lari and Karlberg, Tobias and Helleday, Thomas}},
  issn         = {{1083-351X}},
  keywords     = {{3-Iodobenzylguanidine/pharmacology; Adenosine Diphosphate Ribose/metabolism; Camptothecin/pharmacology; Cell Cycle Proteins/chemistry; 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; Protein Structure, Tertiary; RNA, Small Interfering/metabolism; Topoisomerase I Inhibitors}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{11}},
  pages        = {{60--8054}},
  publisher    = {{American Society for Biochemistry and Molecular Biology}},
  series       = {{The Journal of biological chemistry}},
  title        = {{PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA}},
  url          = {{http://dx.doi.org/10.1074/jbc.M109.077834}},
  doi          = {{10.1074/jbc.M109.077834}},
  volume       = {{285}},
  year         = {{2010}},
}