Ca2+ Activates Human Homologous Recombination Protein Rad51 by Modulating Its ATPase Activity

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. h...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-07, Vol.101 (27), p.9988-9993
Main Authors: Bugreev, Dmitry V., Mazin, Alexander V.
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Adenosine triphosphatases
Adenosine Triphosphatases - metabolism
Adenosine Triphosphate - metabolism
Biochemistry
Biological Sciences
Calcium - pharmacology
DNA
DNA - metabolism
DNA repair
DNA-Binding Proteins - metabolism
Fluorescence
Gels
Gene expression regulation
Hydrolysis
Magnesium - pharmacology
Molecules
Nucleoproteins
Proteins
Rad51 Recombinase
Sodium Chloride - pharmacology
Yeasts
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Summary: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 Mg2+, 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0402105101