User:Deh23/DMC1 (gene)
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[edit]Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the DMC1 gene.[1][2][3][4]
Mutations in this gene are associated with male sterility[5]
RAD51 and DMC1 separated after a gene duplication event in the eukaryote common ancestor.[6]
The presence of DMC1, not its activity is needed during meiosis. RAD51 acts to repair leftover DSBs after interhomolog recombination has occurred. RAD51 activity is down-regulated in budding yeast by inhibition of a Rad51-Rad54 complex through phosphorylation of Hed1 by the meiosis-specific recombinase Mek1.
Structure
[edit]Human DMC1 is a homomultimer in the form of an octameric ring with a diameter of 140 Å and a hole in the middle of 45 Å.[7][8]DMC1 binds preferentially to ssDNA over dsDNA. [7]Unlike RecA and Rad51, DMC1 does not appear to form a helical filament on DNA, instead forming rings with DNA passing through the center.[7] hDMC1 and hRAD51 have 54% amino acid similarity[8] hDMC1 can conduct D-loop formation in supercoiled DNA[9] DMC1 has weak ATPase activity, and is able to promote heteroduplex formation in the presence of a non-hydrolysable analog of ATP, indicating a requirement for ATP binding over ATP hydrolysis. [10]
During meiosis, programmed DNA double strand breaks (DSBs) are introduced by topoisomerase-like enzyme Spo11. DSBs are lengthened through the actions of exonucleases to trim the 5' ends and form long 3' single-stranded DNA (ssDNA) overhangs. These 3' overhangs are stabilized by the effects of single strand binding proteins (SSBs) to protect the ssDNA and prevent the formation of secondary structures. DMC1 is loaded onto the 3' ssDNA to form a right-handed helical nucleoprotein filament. Subsequently, this nucleoprotein filament conducts a homology search in a homologous DNA region. Single-strand invasion in a complementary region in the homologous chromosome by the 3'-ended DNA strand forms a heteroduplex in the form of a displacement loop (D-loop). This D-Loop is extended as DNA repair synthesis occurs, forming a Holliday junction. Resolution of this Holiday junction results in crossover or non-crossover product.[11]
References
[edit]- ^ Habu T, Taki T, West A, Nishimune Y, Morita T (1996). "The mouse and human homologs of DMC1, the yeast meiosis-specific homologous recombination gene, have a common unique form of exon-skipped transcript in meiosis". Nucleic Acids Res. 24 (3): 470–7. doi:10.1093/nar/24.3.470. PMC 145652. PMID 8602360.
- ^ Sato S, Seki N, Hotta Y, Tabata S (1995). "Expression profiles of a human gene identified as a structural homologue of meiosis-specific recA-like genes". DNA Res. 2 (4): 183–6. doi:10.1093/dnares/2.4.183. PMID 8590282.
- ^ Thorslund T, Esashi F, West SC (2007). "Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1". EMBO J. 26 (12): 2915–22. doi:10.1038/sj.emboj.7601739. PMC 1894777. PMID 17541404.
- ^ "Entrez Gene: DMC1 DMC1 dosage suppressor of mck1 homolog, meiosis-specific homologous recombination (yeast)".
- ^ Bannister, Laura A.; Pezza, Roberto J.; Donaldson, Janet R.; Rooij, Dirk G. de; Schimenti, Kerry J.; Camerini-Otero, R. Daniel; Schimenti, John C. (2007-04-10). "A Dominant, Recombination-Defective Allele of Dmc1 Causing Male-Specific Sterility". PLOS Biology. 5 (5): e105. doi:10.1371/journal.pbio.0050105. ISSN 1545-7885.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Da Ines, Olivier; Bazile, Jeanne; Gallego, Maria E.; White, Charles I. (2022-08-25). "DMC1 attenuates RAD51-mediated recombination in Arabidopsis". PLoS Genetics. 18 (8): e1010322. doi:10.1371/journal.pgen.1010322. ISSN 1553-7390. PMC 9451096. PMID 36007010.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c Masson, Jean-Yves; West, Stephen C (2001-02-01). "The Rad51 and Dmc1 recombinases: a non-identical twin relationship". Trends in Biochemical Sciences. 26 (2): 131–136. doi:10.1016/S0968-0004(00)01742-4. ISSN 0968-0004.
- ^ a b Passy, Sophia I.; Yu, Xiong; Li, Zhufang; Radding, Charles M.; Masson, Jean-Yves; West, Stephen C.; Egelman, Edward H. (1999-09-14). "Human Dmc1 protein binds DNA as an octameric ring". Proceedings of the National Academy of Sciences. 96 (19): 10684–10688. doi:10.1073/pnas.96.19.10684. ISSN 0027-8424. PMC 17943. PMID 10485886.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Li, Zhufang; Golub, Efim I.; Gupta, Ravindra; Radding, Charles M. (1997-10-14). "Recombination activities of HsDmc1 protein, the meiotic human homolog of RecA protein". Proceedings of the National Academy of Sciences. 94 (21): 11221–11226. doi:10.1073/pnas.94.21.11221. ISSN 0027-8424. PMC 23422. PMID 9326590.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Masson, Jean-Yves; Davies, Adelina A.; Hajibagheri, Nasser; Van Dyck, Eric; Benson, Fiona E.; Stasiak, Alicja Z.; Stasiak, Andrzej; West, Stephen C. (1999-11-15). "The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51". The EMBO Journal. 18 (22): 6552–6560. doi:10.1093/emboj/18.22.6552. ISSN 0261-4189. PMC 1171718. PMID 10562567.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Da Ines, Olivier; Bazile, Jeanne; Gallego, Maria E.; White, Charles I. (2022-08-25). "DMC1 attenuates RAD51-mediated recombination in Arabidopsis". PLoS Genetics. 18 (8): e1010322. doi:10.1371/journal.pgen.1010322. ISSN 1553-7390. PMC 9451096. PMID 36007010.
{{cite journal}}: CS1 maint: unflagged free DOI (link)