Journal article
Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity
Proceedings of the National Academy of Sciences - PNAS, v 101(27), pp 9988-9993
06 Jul 2004
PMID: 15226506
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 Ca(2+) greatly stimulates DNA strand exchange activity of hRad51 protein. We found that Ca(2+) 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. Ca(2+) 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.
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Details
- Title
- Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity
- Creators
- Dmitry V Bugreev - Department of Biochemistry, Drexel University College of Medicine, Philadelphia, PA 19102-1192, USAAlexander V Mazin
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 101(27), pp 9988-9993
- Publisher
- PNAS; United States
- Grant note
- R56 CA100839 / NCI NIH HHS R01 CA100839 / NCI NIH HHS CA100839 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000222534200010
- Scopus ID
- 2-s2.0-3042791448
- Other Identifier
- 991014878116304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology