Format

Send to

Choose Destination
Nat Commun. 2014 Jul 21;5:4426. doi: 10.1038/ncomms5426.

Family-wide analysis of poly(ADP-ribose) polymerase activity.

Vyas S#1,2, Matic I#3, Uchima L1,2, Rood J1,2, Zaja R4,5, Hay RT3, Ahel I4, Chang P1,2.

Author information

1
Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Sir James Black Centre, Dow Street, Dundee DD1 5EH, UK.
4
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
5
Division for Marine and Environmental Research, Rudjer Boskovic Institute, Zagreb 10002, Croatia.
#
Contributed equally

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.

PMID:
25043379
PMCID:
PMC4123609
DOI:
10.1038/ncomms5426
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center