Formation of meiotic single-stranded DNA invasion complex

Stable Identifier
Reaction [omitted]
Homo sapiens
Formation of Early Recombination Nodule
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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.
Literature References
PubMed ID Title Journal Year
17541404 Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1

West, SC, Esashi, F, Thorslund, T

EMBO J 2007
15164066 Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange

Unger, VM, Bussen, W, Sigurdsson, S, Sehorn, MG, Sung, P

Nature 2004
10562567 The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51

West, SC, Hajibagheri, N, Davies, AA, Masson, JY, Benson, FE, Stasiak, AZ, Stasiak, A, Van Dyck, E

EMBO J 1999
9008167 Association of BRCA1 with Rad51 in mitotic and meiotic cells

Livingston, DM, Scully, R, Feunteun, J, Xiao, Y, Plug, A, Chen, J, Ashley, T, Weaver, D

Cell 1997
17981954 Analysis of replication protein A (RPA) in human spermatogenesis

Turek, PJ, Ko, E, Martin, RH, Oliver-Bonet, M, Campillo, M

Mol Hum Reprod 2007
20062530 Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

Orlova, EV, Hodgkinson, J, Okorokov, AL, Chaban, YL, Bugreev, DV, Mazin, AV

PLoS One 2010
16123081 Temporal progression of recombination in human males

Sun, F, Turek, PJ, Ko, E, Martin, RH, Oliver-Bonet, M

Mol Hum Reprod 2005
9826763 Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA.

Golub, EI, Haaf, T, Radding, CM, Wold, MS, Gupta, RC

Nucleic Acids Res 1999
18535008 A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments

Bishop, DK, Egelman, EH, Sheridan, SD, Roth, R, Yu, X, Sehorn, MG, Heuser, JE, Sung, P

Nucleic Acids Res 2008
9311981 Distribution of the Rad51 recombinase in human and mouse spermatocytes

West, SC, Hultén, MA, Benson, FE, Barlow, AL

EMBO J 1997
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