Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-32428
Altmeyer, M; Messner, S; Hassa, P O; Fey, M; Hottiger, M O (2009). Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. Nucleic Acids Research, 37(11):3723-3738.
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 V(max) and decreased the K(m) 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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology|
|DDC:||570 Life sciences; biology|
|Deposited On:||26 Feb 2010 14:17|
|Last Modified:||28 Nov 2013 01:06|
|Publisher:||Oxford University Press|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 94|
Scopus®. Citation Count: 101
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