Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity

Dmitry V. Bugreev, Alexander V. Mazin

Research output: Contribution to journalArticlepeer-review

192 Scopus citations

Abstract

Human Rad51 (hRad51) protein plays a key role in homologous recombination and DNA repair. hRad51 protein forms a helical filament on single-stranded DNA (ssDNA), which performs the basic steps of homologous recombination: a search for homologous double-stranded DNA (dsDNA) and DNA strand exchange. hRad51 protein possesses DNA-dependent ATPase activity; however, the role of this activity has not been understood. Our current results show that Ca2+ greatly stimulates DNA strand exchange activity of hRad51 protein. We found that Ca2+ exerts its stimulatory effect by modulating the ATPase activity of hRad51 protein. Our data demonstrate that, in the presence of Mg 2+, the hRad51-ATP-ssDNA filament is quickly converted to an inactive hRad51-ADP-ssDNA form, due to relatively rapid ATP hydrolysis and slow dissociation of ADP. Ca2+ maintains the active hRad51-ATP-ssDNA filament by reducing the ATP hydrolysis rate. These findings demonstrate a crucial role of the ATPase activity in regulation of DNA strand exchange activity of hRad51 protein. This mechanism of Rad51 protein regulation by modulating its ATPase activity is evolutionarily recent; we found no such mechanism for yeast Rad51 (yRad51) protein.

Original languageEnglish (US)
Pages (from-to)9988-9993
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number27
DOIs
StatePublished - Jul 6 2004
Externally publishedYes

ASJC Scopus subject areas

  • General

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