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

Proceedings of the National Academy of Sciences of the United States of America
Dmitry V Bugreev, Alexander V Mazin

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.

References

Jan 1, 1991·Annual Review of Biophysics and Biophysical Chemistry·S C Kowalczykowski
Jan 25, 1985·The Journal of Biological Chemistry·F R BryantI R Lehman
May 17, 1984·Nature·P Howard-FlandersA Stasiak
May 1, 1993·Molecular Biology of the Cell·G L SchievenJ A Ledbetter
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·R C GuptaC M Radding
Apr 1, 1997·Current Opinion in Cell Biology·H R Bourne
Jul 1, 1997·The Journal of Laboratory and Clinical Medicine·U GafterH Breitbart
Mar 28, 1998·The EMBO Journal·A V Mazin, S C Kowalczykowski
Aug 11, 1998·Trends in Biochemical Sciences·P Baumann, S C West
Jan 23, 1999·The Journal of Biological Chemistry·E M ZaitsevaS C Kowalczykowski
Mar 29, 2000·Clinical Genetics·T Hassold, S Sherman
Jan 1, 2001·The Journal of Biological Chemistry·S SigurdssonP Sung
Feb 13, 2001·Trends in Biochemical Sciences·J Y Masson, S C West
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
Jul 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·X YuE H Egelman
Feb 13, 2002·The Journal of Biological Chemistry·Gregory TomblineRichard Fishel
Jun 5, 2002·Annual Review of Biochemistry·Shelley L Lusetti, Michael M Cox
Jul 27, 2002·Science·Richard D KolodnerKyungjae Myung
Oct 23, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hye-Kyung KimMasayuki Takahashi
Nov 26, 2002·Nature Structural Biology·Stephen C Kowalczykowski
Jun 5, 2003·Nature Reviews. Molecular Cell Biology·Stephen C West
Jul 31, 2003·Cell·Carsten SchmitzAndrew M Scharenberg
Aug 13, 2003·The Journal of Biological Chemistry·Patrick SungMichael G Sehorn
Mar 23, 2004·Journal of Molecular Biology·Yilun LiuStephen C West
Jun 1, 1993·Current Biology : CB·C M Radding

❮ Previous
Next ❯

Citations

Apr 30, 2013·DNA Repair·William J GrahamCynthia A Haseltine
Sep 11, 2013·Quarterly Reviews of Biophysics·Andrea CandelliGijs J L Wuite
Aug 24, 2010·Nature Structural & Molecular Biology·Jie LiuWolf-Dietrich Heyer
Dec 15, 2010·Nature Structural & Molecular Biology·Dmitry V BugreevAlexander V Mazin
Jul 7, 2011·Nature Structural & Molecular Biology·William K Holloman
Aug 22, 2006·Nature Structural & Molecular Biology·Nami HarutaHiroshi Iwasaki
Jul 31, 2007·Nature Structural & Molecular Biology·Dmitry V BugreevAlexander V Mazin
Apr 19, 2005·Nature Structural & Molecular Biology·Galina V PetukhovaR Daniel Camerini-Otero
Jan 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nayef MazloumWilliam K Holloman
Oct 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Krishanthi JayathilakaPhilip P Connell
Jul 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ragan B RobertsonEric C Greene
Jan 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jovencio HilarioStephen C Kowalczykowski
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthew J RossiAlexander V Mazin
Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Eloïse DrayPatrick Sung
Jun 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Humberto SanchezClaire Wyman
Jul 28, 2009·The Journal of Biological Chemistry·Dmitry V BugreevAlexander V Mazin
Dec 10, 2009·The Journal of Biological Chemistry·Michael G KempMarc S Wold
Apr 2, 2011·The Journal of Biological Chemistry·Naoto AraiTakehiko Shibata
Jan 26, 2012·The Journal of Biological Chemistry·Ravindra AmunugamaRichard Fishel
Jul 12, 2008·The Journal of Biological Chemistry·Matthew J Rossi, Alexander V Mazin
Mar 14, 2008·The Journal of Biological Chemistry·Yun WuStephen C Kowalczykowski
May 23, 2008·The Journal of Biological Chemistry·Dmitry V BugreevAlexander V Mazin
Jan 20, 2009·The Journal of Biological Chemistry·Joshua A SommersRobert M Brosh
May 17, 2013·Journal of Biochemistry·Shalini Verma, Basuthkar J Rao
Aug 18, 2006·Nucleic Acids Research·Mahmud K K ShivjiAshok R Venkitaraman
Apr 12, 2007·Nucleic Acids Research·Mickaël PloquinJean-Yves Masson
Aug 22, 2007·Nucleic Acids Research·Thijn van der HeijdenCees Dekker
Nov 27, 2008·Nucleic Acids Research·Xiao-Ping ZhangWolf-Dietrich Heyer
Feb 27, 2009·Nucleic Acids Research·Joshua N Farb, Scott W Morrical
May 19, 2009·Nucleic Acids Research·Yuichi MorozumiHitoshi Kurumizaka
Nov 26, 2010·Nucleic Acids Research·Evert-Jan UringaSimon J Boulton
Nov 26, 2010·Nucleic Acids Research·Dmitry V BugreevAlexander V Mazin
Nov 28, 2012·Nucleic Acids Research·Scott AtwellGiovanni Cappello
Mar 29, 2013·Nucleic Acids Research·Jessica L SneedenWolf-Dietrich Heyer
Jun 13, 2013·Nucleic Acids Research·Justin A NorthRichard Fishel
Aug 13, 2013·Nucleic Acids Research·Shyamal SubramanyamM Ashley Spies

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.