DNA-dependent SUMO modification of PARP-1.
DNA Repair (Amst)
; 12(9): 761-73, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23871147
ABSTRACT
Poly(ADP-ribose) polymerase 1 (PARP-1) plays an important role in DNA repair, but also contributes to other aspects of nucleic acid metabolism, such as transcriptional regulation. Modification of PARP-1 with the small ubiquitin-related modifier (SUMO) affects its function as a transcriptional co-activator of hypoxia-responsive genes and promotes induction of the heat shock-induced HSP70.1 promoter. We now report that PARP-1 sumoylation is strongly influenced by DNA. Consistent with a function in transcription, we show that sumoylation in vitro is enhanced by binding to intact, but not to damaged DNA, in a manner clearly distinct from the mechanism by which DNA damage stimulates PARP-1's catalytic activity. An enhanced affinity of PARP-1 for the SUMO-conjugating enzyme Ubc9 upon binding to DNA is likely responsible for this effect. Sumoylation does not interfere with the catalytic or DNA-binding properties of PARP-1, and structural analysis reveals no significant impact of SUMO on the conformation of PARP-1's DNA-binding domain. In vivo, sumoylated PARP-1 is associated with chromatin, but the modification is not responsive to DNA damage and is not affected by PARP-1 catalytic activity. Our results suggest that PARP-1's alternative modes of DNA recognition serve as a means to differentiate between distinct aspects of the enzyme's function.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Poli(ADP-Ribose) Polimerases
/
Proteína SUMO-1
/
Sumoilação
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article