title: Family-wide analysis of poly(ADP-ribose) polymerase activity.
abstract: The poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) protein family generates ADP-ribose (ADPr) modifications onto target proteins using NAD(+) as substrate. Based on the composition of three NAD(+) coordinating amino acids, the H-Y-E motif, each PARP is predicted to generate either poly(ADPr) (PAR) or mono(ADPr) (MAR). However, the reaction product of each PARP has not been clearly defined, and is an important priority since PAR and MAR function via distinct mechanisms. Here we show that the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity. We identify automodification sites on seven PARPs, and demonstrate that MAR and PAR generating PARPs modify similar amino acids, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets. In addition, we identify cysteine as a novel amino-acid target for ADP-ribosylation on PARPs.
authors.affiliation: Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sejal
authors.initials: S
authors.lastname: Vyas
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Matic
authors.affiliation: Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Lilen
authors.initials: L
authors.lastname: Uchima
authors.affiliation: Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Rood
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.|Division for Marine and Environmental Research, Rudjer Boskovic Institute, Zagreb 10002, Croatia.
authors.forename: Roko
authors.initials: R
authors.lastname: Zaja
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee DD1 5EH, UK.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ahel
authors.affiliation: Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Chang
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D020816:Amino Acid Motifs; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000246:Adenosine Diphosphate Ribose; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; D008239:Lysine; D003545:Cysteine