Skip Navigation


Nucleic Acids Research Advance Access originally published online on April 16, 2009
Nucleic Acids Research 2009 37(11):3723-3738; doi:10.1093/nar/gkp229
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (9554K) Freely available
Right arrow Screen PDF (797K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
37/11/3723    most recent
gkp229v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Altmeyer, M.
Right arrow Articles by Hottiger, M. O.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Altmeyer, M.
Right arrow Articles by Hottiger, M. O.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2009, Vol. 37, No. 11 3723-3738
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Nucleic Acids Enzymes

Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites

Matthias Altmeyer1,2, Simon Messner1,2, Paul O. Hassa3, Monika Fey1 and Michael O. Hottiger1,*

1Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland, 2Life Science Zurich Graduate School, Molecular Life Science Program, University of Zurich and 3European Molecular Biology Laboratory (EMBL), Gene Expression Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany

*To whom correspondence should be addressed. Tel: +41 44 635 54 74; Fax: +41 44 635 68 40; Email: hottiger{at}vetbio.uzh.ch

Received January 14, 2009. Revised March 9, 2009. Accepted March 24, 2009.

Poly(ADP-ribose) polymerase 1 (PARP1) synthesizes poly(ADP-ribose) (PAR) using nicotinamide adenine dinucleotide (NAD) as a substrate. Despite intensive research on the cellular functions of PARP1, the molecular mechanism of PAR formation has not been comprehensively understood. In this study, we elucidate the molecular mechanisms of poly(ADP-ribosyl)ation and identify PAR acceptor sites. Generation of different chimera proteins revealed that the amino-terminal domains of PARP1, PARP2 and PARP3 cooperate tightly with their corresponding catalytic domains. The DNA-dependent interaction between the amino-terminal DNA-binding domain and the catalytic domain of PARP1 increased Vmax and decreased the Km for NAD. Furthermore, we show that glutamic acid residues in the auto-modification domain of PARP1 are not required for PAR formation. Instead, we identify individual lysine residues as acceptor sites for ADP-ribosylation. Together, our findings provide novel mechanistic insights into PAR synthesis with significant relevance for the different biological functions of PARP family members.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
S. Messner, D. Schuermann, M. Altmeyer, I. Kassner, D. Schmidt, P. Schar, S. Muller, and M. O. Hottiger
Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function
FASEB J, November 1, 2009; 23(11): 3978 - 3989.
[Abstract] [Full Text] [PDF]

Home page
 Plant Physiol.Home page
S. Teotia and R. S. Lamb
The Paralogous Genes RADICAL-INDUCED CELL DEATH1 and SIMILAR TO RCD ONE1 Have Partially Redundant Functions during Arabidopsis Development
Plant Physiology, September 1, 2009; 151(1): 180 - 198.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.