期刊
DNA REPAIR
卷 12, 期 9, 页码 761-773出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2013.07.001
关键词
PARP-1; SUMO; Posttranslational modification; DNA binding; DNA repair; Transcription
资金
- Cancer Research UK
- Medical Research Council [U105178934]
- Association for International Cancer Research
- Boehringer Ingelheim Foundation
- MRC [MC_U105178934] Funding Source: UKRI
- Cancer Research UK [11582] Funding Source: researchfish
- Medical Research Council [MC_U105178934] Funding Source: researchfish
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. (c) 2013 The Authors. Published by Elsevier B.V. All rights reserved.
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