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Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity

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Bugreev, Dmitry V., Mazin, Alexander V.·2004·Proceedings of the National Academy of Sciences

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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Metadata

Authors
Bugreev, D. V., & Mazin, A. V.
Venue
Proceedings of the National Academy of Sciences
Published
2004-06-28
Volume
101
Issue
27
Pages
9988-9993
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2154074565
Cited by
245
References
1
FWCI
4.37
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. https://app.cochat.ai/papers/10.1073/pnas.0402105101
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Bugreev, D. V., & Mazin, A. V. (2004). Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402105101

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