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

@article{Altmeyer09, abstract = {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.}, author = {Altmeyer, M. and Messner, S. and Hassa, P. O. and Fey, M. and Hottiger, M. O.}, citeulike-article-id = {5206078}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/nar/gkp229}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19372272}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19372272}, doi = {10.1093/nar/gkp229}, issn = {1362-4962}, journal = {Nucleic acids research}, keywords = {kinetic, parp1}, month = {June}, number = {11}, pages = {3723--3738}, posted-at = {2009-07-20 03:38:08}, priority = {2}, title = {Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites.}, url = {http://dx.doi.org/10.1093/nar/gkp229}, volume = {37}, year = {2009} }

TY - JOUR ID - Altmeyer09 L3 - citeulike-article-id:5206078 N2 - 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. IS - 11 JF - Nucleic acids research SN - 1362-4962 EP - 3738 TI - Molecular mechanism of poly(ADP-ribosyl)ation by PARP1 and identification of lysine residues as ADP-ribose acceptor sites. VL - 37 SP - 3723 KW - kinetic KW - parp1 AU - Altmeyer, M AU - Messner, S AU - Hassa, PO AU - Fey, M AU - Hottiger, MO PY - 2009/06// UR - http://dx.doi.org/10.1093/nar/gkp229 ER -