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Formation of meiotic single-stranded DNA invasion complex
Stable identifierREACT_27160.2
AuthoredMay, B, 2010-07-19
ReviewedBolcun-Filas, E, 2011-02-25
Cohen, PE, 2011-02-04
Holloway, JK, 2011-02-04
Lyndaker, A, 2011-02-25
Schimenti, JC, 2011-02-04
Strong, E, 2011-02-25
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Two RecA homologs, RAD51 and the meiosis-specific DMC1, coat single-stranded 3' ends of DNA produced by resection of double-strand breaks (Barlow et al. 1997, Masson et al. 1999, Sehorn et al. 2004, Sheridan et al. 2008, Okorokov et al. 2010). RAD51 and DMC1 interact and colocalize to the same early recombination nodules (Masson et al. 1999). Knockouts of DMC1 abolish recombination and synapsis therefore RAD51 is not sufficient for recombination.
Immunocytology shows the RPA heterotrimer arrives at recombination nodules with or after RAD51 and DMC1 (Golub et al. 1999, Oliver-Bonet et al. 2005, Oliver-Bonet et al. 2007)). (In mitotic recombination RPA precedes RAD51.)
BRCA1 and BRCA2 are found extensively distributed on synaptonemal complexes. Results from human cells and knockout mice indicate that BRCA2, RAD51C, and TEX15 participate in loading RAD51 and DMC1 onto single-stranded DNA (Thorslund et al. 2007). BRCA1 participates in loading RAD51 but not DMC1 (Scully et al. 1997).
The kinase ATM is also localized to double-strand breaks where it phosphorylates histone H2AX.
In human spermatocytes about 350 early recombination nodules form but only about 10% will continue on to make crossovers. The remaining 90% are believed to be resolved by synthesis-dependent strand annealing, which transfers short segments of DNA (about 0.2-2.0 kilobases) between homologs.
Input (present at start of reaction)BRCA2 [nucleoplasm] UKENBCdOOOOORHPGPURD
RAD51 [nucleoplasm] UKENBCdOOORHPGPPURDD
DMC1 [nucleoplasm] UKENBCdORHPGPURD
ATM [nucleoplasm] UKENNBBCCddOOORHPGURRZ
RPA heterotrimer [nucleoplasm]
3' overhanging DNA at resected DSB ends [nucleoplasm]
BRCA1 [nucleoplasm] UKENBCdOOORRRHHHPGPPPPPPPPPURRRRDDDDDDDDDZ
CDK4 [nucleoplasm] UKENBCdOOOORHPGPURDZ
Nucleosome with Histone H2A.x [nucleoplasm]
Output (present at end of reaction)Meiotic single-stranded DNA complex [nucleoplasm]
Preceding event(s)MRN:CtIP hydrolyzes single-strand DNA 3' to SPO11 and SPO11:double-strand break dissociates to SPO11:oligonucleotide and resected 5' end [Homo sapiens]
Following event(s)Formation of meiotic heteroduplex [Homo sapiens]
OrganismHomo sapiens
Cellular compartmentnucleoplasm GO
Positively regulated byTEX15 [nucleoplasm] UKENBCdORHPGUR
RAD51C [nucleoplasm] UKENBCdOORRHHPGURR
References

Thorslund, T, Esashi, F, West, SC Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1 2007 EMBO J PubMed

Scully, R, Chen, J, Plug, A, Xiao, Y, Weaver, D, Feunteun, J, Ashley, T, Livingston, DM Association of BRCA1 with Rad51 in mitotic and meiotic cells 1997 Cell PubMed

Oliver-Bonet, M, Campillo, M, Turek, PJ, Ko, E, Martin, RH Analysis of replication protein A (RPA) in human spermatogenesis 2007 Mol Hum Reprod PubMed

Sheridan, SD, Yu, X, Roth, R, Heuser, JE, Sehorn, MG, Sung, P, Egelman, EH, Bishop, DK A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments 2008 Nucleic Acids Res PubMed

Golub, EI, Gupta, RC, Haaf, T, Wold, MS, Radding, CM Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA. 1999 Nucleic Acids Res PubMed

Masson, JY, Davies, AA, Hajibagheri, N, Van Dyck, E, Benson, FE, Stasiak, AZ, Stasiak, A, West, SC The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51 1999 EMBO J PubMed

Okorokov, AL, Chaban, YL, Bugreev, DV, Hodgkinson, J, Mazin, AV, Orlova, EV Structure of the hDmc1-ssDNA filament reveals the principles of its architecture 2010 PLoS One PubMed

Oliver-Bonet, M, Turek, PJ, Sun, F, Ko, E, Martin, RH Temporal progression of recombination in human males 2005 Mol Hum Reprod PubMed

Barlow, AL, Benson, FE, West, SC, Hultén, MA Distribution of the Rad51 recombinase in human and mouse spermatocytes 1997 EMBO J PubMed

Sehorn, MG, Sigurdsson, S, Bussen, W, Unger, VM, Sung, P Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange 2004 Nature PubMed

This event is deduced on the basis of event(s)Formation of Meiotic Single-stranded Invasion Complex [Mus musculus]
Equivalent event(s) in other organism(s)Formation of meiotic single-stranded DNA invasion complex [Sus scrofa]
Formation of meiotic single-stranded DNA invasion complex [Bos taurus]
Formation of meiotic single-stranded DNA invasion complex [Canis familiaris]
Formation of meiotic single-stranded DNA invasion complex [Rattus norvegicus]
Participating molecules
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REACT_27160