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DNA repair factor MRE11/RAD50 cleaves 3'-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons.

ABSTRACT: MRE11-RAD50 is a highly conserved multifunctional DNA repair factor. Here, we show that MRE11-RAD50 cleaves the covalent 3'-phosphotyrosyl-DNA bonds that join topoisomerase 1 (Top1) to the DNA backbone and that are the hallmark of damage caused by Top1 poisons such as camptothecin. Cleavage generates a 3'-phosphate DNA end that MRE11-RAD50 can resect in an ATP-regulated reaction, to produce a 3'-hydroxyl that can prime repair synthesis. The 3'-phosphotyrosyl cleavage activity maps to the MRE11 active site. These results define a new activity of MRE11 and distinguish MRE11-RAD50 functions in repair of Top1-DNA complexes and double-strand breaks.

SUBMITTER: Sacho EJ

PROVIDER: S-EPMC3247996 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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DNA repair factor MRE11/RAD50 cleaves 3'-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons.

Sacho Elizabeth J EJ Maizels Nancy N

The Journal of biological chemistry 20111028 52

MRE11-RAD50 is a highly conserved multifunctional DNA repair factor. Here, we show that MRE11-RAD50 cleaves the covalent 3'-phosphotyrosyl-DNA bonds that join topoisomerase 1 (Top1) to the DNA backbone and that are the hallmark of damage caused by Top1 poisons such as camptothecin. Cleavage generates a 3'-phosphate DNA end that MRE11-RAD50 can resect in an ATP-regulated reaction, to produce a 3'-hydroxyl that can prime repair synthesis. The 3'-phosphotyrosyl cleavage activity maps to the MRE11 a ...[more]

PMID: 22039049

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