Role of poly(ADP-ribose) formation in DNA repair
- PMID: 1549180
- DOI: 10.1038/356356a0
Role of poly(ADP-ribose) formation in DNA repair
Abstract
The abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+). This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD(+)-binding domain by a short region containing several glutamic acid residues that are sites of auto-poly(ADP-ribosyl)ation. The intracellular production of poly(ADP-ribose) is induced by agents that generate strand interruptions in DNA. The branched homopolymer chains may attain a size of 200-300 residues but are rapidly degraded after synthesis. The function of poly(ADP-ribose) synthesis is not clear, although it seems to be required for DNA repair. Here we describe a human cell-free system that enables the role of poly(ADP-ribose) synthesis in DNA repair to be characterized. The results indicate that unmodified polymerase molecules bind tightly to DNA strand breaks; auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes.
Similar articles
-
Poly(ADP-ribose) synthesis in blocked and damaged cells and its relation to carcinogenesis.Anticancer Res. 1992 May-Jun;12(3):885-98. Anticancer Res. 1992. PMID: 1535771
-
Protein-protein interaction of the human poly(ADP-ribosyl)transferase depends on the functional state of the enzyme.Biochemistry. 1997 Jun 17;36(24):7297-304. doi: 10.1021/bi962710g. Biochemistry. 1997. PMID: 9200678
-
Poly(ADP-ribose) in the cellular response to DNA damage.Radiat Res. 1985 Jan;101(1):4-15. Radiat Res. 1985. PMID: 3155867 Review.
-
A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage.Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9886-91. doi: 10.1073/pnas.170280397. Proc Natl Acad Sci U S A. 2000. PMID: 10944198 Free PMC article.
-
Relation between carcinogenesis, chromatin structure and poly(ADP-ribosylation) (review).Anticancer Res. 1991 Mar-Apr;11(2):489-527. Anticancer Res. 1991. PMID: 1905900 Review.
Cited by
-
SRY (sex determining region Y)-box2 (Sox2)/poly ADP-ribose polymerase 1 (Parp1) complexes regulate pluripotency.Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3772-7. doi: 10.1073/pnas.1108595109. Epub 2012 Feb 23. Proc Natl Acad Sci U S A. 2012. PMID: 22362888 Free PMC article.
-
Regulation of chromatin structure by poly(ADP-ribosyl)ation.Front Genet. 2012 Sep 3;3:169. doi: 10.3389/fgene.2012.00169. eCollection 2012. Front Genet. 2012. PMID: 22969794 Free PMC article.
-
MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation.Invest New Drugs. 2012 Dec;30(6):2113-20. doi: 10.1007/s10637-011-9770-x. Epub 2011 Nov 30. Invest New Drugs. 2012. PMID: 22127459
-
Quercitrin protects skin from UVB-induced oxidative damage.Toxicol Appl Pharmacol. 2013 Jun 1;269(2):89-99. doi: 10.1016/j.taap.2013.03.015. Epub 2013 Mar 29. Toxicol Appl Pharmacol. 2013. PMID: 23545178 Free PMC article.
-
Frankincense essential oil prepared from hydrodistillation of Boswellia sacra gum resins induces human pancreatic cancer cell death in cultures and in a xenograft murine model.BMC Complement Altern Med. 2012 Dec 13;12:253. doi: 10.1186/1472-6882-12-253. BMC Complement Altern Med. 2012. PMID: 23237355 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources