Meiotic recombination (Homo sapiens)

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Bibliography

1. Benson FE, Baumann P, West SC.; ''Synergistic actions of Rad51 and Rad52 in recombination and DNA repair.''; PubMed Europe PMC Scholia
2. 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.''; PubMed Europe PMC Scholia
3. Murayama Y, Kurokawa Y, Mayanagi K, Iwasaki H.; ''Formation and branch migration of Holliday junctions mediated by eukaryotic recombinases.''; PubMed Europe PMC Scholia
4. Oliver-Bonet M, Turek PJ, Sun F, Ko E, Martin RH.; ''Temporal progression of recombination in human males.''; PubMed Europe PMC Scholia
5. Okorokov AL, Chaban YL, Bugreev DV, Hodgkinson J, Mazin AV, Orlova EV.; ''Structure of the hDmc1-ssDNA filament reveals the principles of its architecture.''; PubMed Europe PMC Scholia
6. Santucci-Darmanin S, Walpita D, Lespinasse F, Desnuelle C, Ashley T, Paquis-Flucklinger V.; ''MSH4 acts in conjunction with MLH1 during mammalian meiosis.''; PubMed Europe PMC Scholia
7. Hayashi K, Yoshida K, Matsui Y.; ''A histone H3 methyltransferase controls epigenetic events required for meiotic prophase.''; PubMed Europe PMC Scholia
8. Oliver-Bonet M, Campillo M, Turek PJ, Ko E, Martin RH.; ''Analysis of replication protein A (RPA) in human spermatogenesis.''; PubMed Europe PMC Scholia
9. Snowden T, Acharya S, Butz C, Berardini M, Fishel R.; ''hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes.''; PubMed Europe PMC Scholia
10. Snowden T, Shim KS, Schmutte C, Acharya S, Fishel R.; ''hMSH4-hMSH5 adenosine nucleotide processing and interactions with homologous recombination machinery.''; PubMed Europe PMC Scholia
11. Barlow AL, Hultén MA.; ''Crossing over analysis at pachytene in man.''; PubMed Europe PMC Scholia
12. 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.''; PubMed Europe PMC Scholia
13. Johnson FB, Lombard DB, Neff NF, Mastrangelo MA, Dewolf W, Ellis NA, Marciniak RA, Yin Y, Jaenisch R, Guarente L.; ''Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.''; PubMed Europe PMC Scholia
14. Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L, May CA, Jeffreys AJ.; ''PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.''; PubMed Europe PMC Scholia
15. Cohen PE, Pollack SE, Pollard JW.; ''Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals.''; PubMed Europe PMC Scholia
16. Baumann P, West SC.; ''Heteroduplex formation by human Rad51 protein: effects of DNA end-structure, hRP-A and hRad52.''; PubMed Europe PMC Scholia
17. Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID.; ''The Bloom's syndrome gene product interacts with topoisomerase III.''; PubMed Europe PMC Scholia
18. Handel MA, Schimenti JC.; ''Genetics of mammalian meiosis: regulation, dynamics and impact on fertility.''; PubMed Europe PMC Scholia
19. Sehorn MG, Sigurdsson S, Bussen W, Unger VM, Sung P.; ''Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange.''; PubMed Europe PMC Scholia
20. Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, Przeworski M, Coop G, de Massy B.; ''PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice.''; PubMed Europe PMC Scholia
21. Cannavo E, Marra G, Sabates-Bellver J, Menigatti M, Lipkin SM, Fischer F, Cejka P, Jiricny J.; ''Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair.''; PubMed Europe PMC Scholia
22. Myers S, Bowden R, Tumian A, Bontrop RE, Freeman C, MacFie TS, McVean G, Donnelly P.; ''Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination.''; PubMed Europe PMC Scholia
23. Baumann P, Benson FE, West SC.; ''Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro.''; PubMed Europe PMC Scholia
24. Sartori AA, Lukas C, Coates J, Mistrik M, Fu S, Bartek J, Baer R, Lukas J, Jackson SP.; ''Human CtIP promotes DNA end resection.''; PubMed Europe PMC Scholia
25. Kondo E, Horii A, Fukushige S.; ''The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2.''; PubMed Europe PMC Scholia
26. Thorslund T, Esashi F, West SC.; ''Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1.''; PubMed Europe PMC Scholia
27. 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.''; PubMed Europe PMC Scholia
28. Inagaki A, Schoenmakers S, Baarends WM.; ''DNA double strand break repair, chromosome synapsis and transcriptional silencing in meiosis.''; PubMed Europe PMC Scholia
29. Enomoto R, Kinebuchi T, Sato M, Yagi H, Kurumizaka H, Yokoyama S.; ''Stimulation of DNA strand exchange by the human TBPIP/Hop2-Mnd1 complex.''; PubMed Europe PMC Scholia
30. Barlow AL, Benson FE, West SC, Hultén MA.; ''Distribution of the Rad51 recombinase in human and mouse spermatocytes.''; PubMed Europe PMC Scholia
31. Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R.; ''hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis.''; PubMed Europe PMC Scholia
32. Golub EI, Gupta RC, Haaf T, Wold MS, Radding CM.; ''Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
3' overhanging DNA at resected DSB ends		R-NUL-75156 (Reactome)
3' overhanging DNA at resected DSB ends		R-NUL-75156 (Reactome)
ATM	Protein	Q13315 (Uniprot-TrEMBL)
ATM	Protein	Q13315 (Uniprot-TrEMBL)
AdoHcy	Metabolite	CHEBI:16680 (ChEBI)
AdoMet	Metabolite	CHEBI:15414 (ChEBI)
BLM	Protein	P54132 (Uniprot-TrEMBL)
BLM	Protein	P54132 (Uniprot-TrEMBL)
BRCA1	Protein	P38398 (Uniprot-TrEMBL)
BRCA1	Protein	P38398 (Uniprot-TrEMBL)
BRCA2	Protein	P51587 (Uniprot-TrEMBL)
BRCA2	Protein	P51587 (Uniprot-TrEMBL)
CDK2	Protein	P24941 (Uniprot-TrEMBL)
CDK2	Protein	P24941 (Uniprot-TrEMBL)
CDK4	Protein	P11802 (Uniprot-TrEMBL)
CDK4	Protein	P11802 (Uniprot-TrEMBL)
Cleaved Meiotic Holliday Junction	Complex	R-HSA-913201 (Reactome)
DMC1	Protein	Q14565 (Uniprot-TrEMBL)
DMC1	Protein	Q14565 (Uniprot-TrEMBL)
DNA		R-NUL-29428 (Reactome)
DNA double-strand break ends		R-NUL-75165 (Reactome)
DNA		R-NUL-29428 (Reactome)
H2AFB1	Protein	P0C5Y9 (Uniprot-TrEMBL)
H2AFX	Protein	P16104 (Uniprot-TrEMBL)
H2AFX-Nucleosome	Complex	R-HSA-975775 (Reactome)
H2AFZ	Protein	P0C0S5 (Uniprot-TrEMBL)
H2BFS	Protein	P57053 (Uniprot-TrEMBL)
HIST1H2AB	Protein	P04908 (Uniprot-TrEMBL)
HIST1H2AC	Protein	Q93077 (Uniprot-TrEMBL)
HIST1H2AD	Protein	P20671 (Uniprot-TrEMBL)
HIST1H2AJ	Protein	Q99878 (Uniprot-TrEMBL)
HIST1H2BA	Protein	Q96A08 (Uniprot-TrEMBL)
HIST1H2BB	Protein	P33778 (Uniprot-TrEMBL)
HIST1H2BC	Protein	P62807 (Uniprot-TrEMBL)
HIST1H2BD	Protein	P58876 (Uniprot-TrEMBL)
HIST1H2BH	Protein	Q93079 (Uniprot-TrEMBL)
HIST1H2BJ	Protein	P06899 (Uniprot-TrEMBL)
HIST1H2BK	Protein	O60814 (Uniprot-TrEMBL)
HIST1H2BL	Protein	Q99880 (Uniprot-TrEMBL)
HIST1H2BM	Protein	Q99879 (Uniprot-TrEMBL)
HIST1H2BN	Protein	Q99877 (Uniprot-TrEMBL)
HIST1H2BO	Protein	P23527 (Uniprot-TrEMBL)
HIST1H4	Protein	P62805 (Uniprot-TrEMBL)
HIST2H2AA3	Protein	Q6FI13 (Uniprot-TrEMBL)
HIST2H2AC	Protein	Q16777 (Uniprot-TrEMBL)
HIST2H2BE	Protein	Q16778 (Uniprot-TrEMBL)
HIST3H2BB	Protein	Q8N257 (Uniprot-TrEMBL)
HIST3H3	Protein	Q16695 (Uniprot-TrEMBL)
HOP2(TBPIP):MND1	Complex	R-HSA-913509 (Reactome)
Heteroduplex DNA containing D-loop structure		R-NUL-83891 (Reactome)
Holliday structure		R-NUL-75220 (Reactome)
MLH1	Protein	P40692 (Uniprot-TrEMBL)
MLH1	Protein	P40692 (Uniprot-TrEMBL)
MLH3	Protein	Q9UHC1 (Uniprot-TrEMBL)
MLH3	Protein	Q9UHC1 (Uniprot-TrEMBL)
MND1	Protein	Q9BWT6 (Uniprot-TrEMBL)
MRE11A	Protein	P49959 (Uniprot-TrEMBL)
MRN:CtIP	Complex	R-HSA-981776 (Reactome)
MSH4	Protein	O15457 (Uniprot-TrEMBL)
MSH4	Protein	O15457 (Uniprot-TrEMBL)
MSH5	Protein	O43196 (Uniprot-TrEMBL)
MSH5	Protein	O43196 (Uniprot-TrEMBL)
Me2K5-H3F3A	Protein	P84243 (Uniprot-TrEMBL)
Me2K5-HIST1H3A	Protein	P68431 (Uniprot-TrEMBL)
Me2K5-HIST2H3A	Protein	Q71DI3 (Uniprot-TrEMBL)
Me3K5-H3F3A	Protein	P84243 (Uniprot-TrEMBL)
Me3K5-HIST1H3A	Protein	P68431 (Uniprot-TrEMBL)
Me3K5-HIST2H3A	Protein	Q71DI3 (Uniprot-TrEMBL)
Meiotic single-stranded DNA complex	Complex	R-HSA-912507 (Reactome)
Meiotic D-loop complex	Complex	R-HSA-912484 (Reactome)
Meiotic Holliday Junction	Complex	R-HSA-912428 (Reactome)
NBN	Protein	O60934 (Uniprot-TrEMBL)
Nucleosome with H3K4me2	Complex	R-HSA-1214200 (Reactome)
Nucleosome with H3K4me3	Complex	R-HSA-1214169 (Reactome)
PRDM9	Protein	Q9NQV7 (Uniprot-TrEMBL)
PRDM9:DNA	Complex	R-HSA-912415 (Reactome)
PRDM9	Protein	Q9NQV7 (Uniprot-TrEMBL)
PSMC3IP	Protein	Q9P2W1 (Uniprot-TrEMBL)
RAD50	Protein	Q92878 (Uniprot-TrEMBL)
RAD51	Protein	Q06609 (Uniprot-TrEMBL)
RAD51C	Protein	O43502 (Uniprot-TrEMBL)
RAD51	Protein	Q06609 (Uniprot-TrEMBL)
RBBP8	Protein	Q99708 (Uniprot-TrEMBL)
RPA heterotrimer	Complex	R-HSA-68462 (Reactome)
RPA1	Protein	P27694 (Uniprot-TrEMBL)
RPA2	Protein	P15927 (Uniprot-TrEMBL)
RPA3	Protein	P35244 (Uniprot-TrEMBL)
SPO11 Dimer	Complex	R-HSA-912393 (Reactome)
SPO11	Protein	Q9Y5K1 (Uniprot-TrEMBL)
SPO11:double stand break	Complex	R-HSA-912365 (Reactome)	The gene encoding SPO11 shares sequence similarity to TopoVI, a type II topoisomerase. SPO11 dimers cleave both strands of DNA. Each subunit of the dimer remains covalently attached to the 5' end of one strand of DNA via a phosphodiester linkage to a conserved tyrosine residue of SPO11. In addition to SPO11, work from budding yeast has shown a total of 7 proteins essential for double strand break formation. The mammalian ortholog of Mei4 (S. cerevisiae) as well as a mammalian-specific gene called Mei1 are essential to formation of meiotic double strand breaks.
SPO11:oligonucleotide	Complex	R-HSA-912381 (Reactome)
Single-Stranded Oligodeoxyribonucleotide (12 to 34 nucleotides)		R-NUL-912367 (Reactome)
TEX15	Protein	Q9BXT5 (Uniprot-TrEMBL)
TOP3A	Protein	Q13472 (Uniprot-TrEMBL)
TOP3A	Protein	Q13472 (Uniprot-TrEMBL)
cleaved Holliday structure		R-NUL-83636 (Reactome)
p-S139-H2AFX	Protein	P16104 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	3' overhanging DNA at resected DSB ends	Arrow	R-HSA-912397 (Reactome)
3' overhanging DNA at resected DSB ends			R-HSA-912503 (Reactome)
ATM			R-HSA-912503 (Reactome)
	AdoHcy	Arrow	R-HSA-1214188 (Reactome)
AdoMet			R-HSA-1214188 (Reactome)
	BLM	Arrow	R-HSA-912429 (Reactome)
BLM			R-HSA-912496 (Reactome)
BRCA1			R-HSA-912503 (Reactome)
	BRCA2	Arrow	R-HSA-912429 (Reactome)
BRCA2			R-HSA-912503 (Reactome)
CDK2			R-HSA-912429 (Reactome)
	CDK4	Arrow	R-HSA-912429 (Reactome)
CDK4			R-HSA-912503 (Reactome)
	Cleaved Meiotic Holliday Junction	Arrow	R-HSA-912429 (Reactome)
	DMC1	Arrow	R-HSA-912496 (Reactome)
DMC1			R-HSA-912503 (Reactome)
DNA			R-HSA-912363 (Reactome)
DNA			R-HSA-912368 (Reactome)
DNA			R-HSA-912458 (Reactome)
H2AFX-Nucleosome			R-HSA-912503 (Reactome)
HOP2(TBPIP):MND1		Arrow	R-HSA-912458 (Reactome)
MLH1			R-HSA-912429 (Reactome)
MLH3			R-HSA-912429 (Reactome)
MRN:CtIP		mim-catalysis	R-HSA-912397 (Reactome)
	MSH4	Arrow	R-HSA-912429 (Reactome)
MSH4			R-HSA-912496 (Reactome)
	MSH5	Arrow	R-HSA-912429 (Reactome)
MSH5			R-HSA-912496 (Reactome)
	Meiotic single-stranded DNA complex	Arrow	R-HSA-912503 (Reactome)
Meiotic single-stranded DNA complex			R-HSA-912458 (Reactome)
Meiotic single-stranded DNA complex		mim-catalysis	R-HSA-912458 (Reactome)
	Meiotic D-loop complex	Arrow	R-HSA-912458 (Reactome)
Meiotic D-loop complex			R-HSA-912496 (Reactome)
	Meiotic Holliday Junction	Arrow	R-HSA-912496 (Reactome)
Meiotic Holliday Junction			R-HSA-912429 (Reactome)
Nucleosome with H3K4me2			R-HSA-1214188 (Reactome)
	Nucleosome with H3K4me3	Arrow	R-HSA-1214188 (Reactome)
	PRDM9:DNA	Arrow	R-HSA-912363 (Reactome)
PRDM9:DNA		mim-catalysis	R-HSA-1214188 (Reactome)
PRDM9			R-HSA-912363 (Reactome)
			R-HSA-1214188 (Reactome)	As inferred from experiments in vitro with mouse Prdm9, human PRDM9 methylates histone H3 dimethylated at lysine-4 to yield histone H3 trimethylated at lysine-4.
			R-HSA-912363 (Reactome)	PR-domain containing 9 (PRDM9) protein is a meiosis specific histone H3 lysine 4 (H3K4) methyltransferase, with a zinc finger domain at the C-terminus. Meiotic recombination hotspots in humans and mice are known to be sites for histone modification. PRDM9 has been shown to affect recombination profiles and meiotic recombination hotspot activity, by binding specific sequence motifs within or close to recombination hotspots (Baudat et al. 2010, Myers et al. 2010), and reorganizing chromatin structure. Variation within this protein has been proven to negatively affect human male fertility, with certain patients harboring variants at the PRDM9 locus exhibiting azoospermia. PRDM9 recognizes a specific sequence motif, but also acts at human hotspots lacking the motif, suggesting it is capable of acting in cis to regulate hotspot activity. These specific sequence motifs also appear to be species specific, as the degenerate 13-bp motif associated with 40% of human hotspots does not function in chimpanzees, probably as a result of the rapidly evolving zinc finger domain (Myers et al. 2010). Subtle changes in the zinc finger array in humans can have global effects on recombination throughout the human genome, enhancing or decreasing the activity of a hotspot, or even creating entirely new hotspots (Berg et al. 2010). In addition to its role in regulating recombination hotspot activity, PRDM9 also appears to have a role in maintaining stability within the human genome, as variation in the PRDM9 gene can lead to large-scale genomic rearrangements and minisatellite instability in humans.
			R-HSA-912368 (Reactome)	The gene encoding SPO11 shares sequence similarity to TopoVI, a type II topoisomerase. SPO11 dimers cleave both strands of DNA. Each subunit of the dimer remains covalently attached to the 5' end of one strand of DNA via a phosphodiester linkage to a conserved tyrosine residue of SPO11. In addition to SPO11, work from budding yeast has shown a total of 7 proteins essential for double strand break formation. The mammalian ortholog of Mei4 (S. cerevisiae) as well as a mammalian-specific gene called Mei1 are essential to formation of meiotic double strand breaks.
			R-HSA-912397 (Reactome)	SPO11 forms a dimer and each subunit cleaves a single strand of DNA, thus creating a double-strand break. After cleaving DNA, a SPO11 subunit remains covalently attached to each 5' end via a tyrosine residue. SPO11 is removed from the DNA by cleavage of single strands 3' to the attached SPO11. The products are a resected 5' end (protruding 3' overhang) and a covalent complex of SPO11 with an oligonucleotide. Two size classes of oligonucleotide are observed: 12 to 26 nucleotides and 28 to 34 nucleotides. The enzyme responsible for excision of SPO11:oligonucleotide in mammals is inferred to be MRE11 in the MRE11:RAD50:NBS1:CtIP complex based on conservation of the reaction mechanism across yeast, plants, and animals (Sartori et al. 2007). In fission and budding yeast the Mre11:Rad50:Xrs2/Nbs1 (MRN/MRX) complex is required for removal of SPO11. In human somatic cells the MRN complex together with CtIP resects double-strand breaks in somatic cells but the role of the MRN complex in mammalian meiosis, though essential, is unclear (Sartori et al. 2007). After excision of SPO11:oligonucleotide the recessed 5' end is further resected by unknown exonucleases.
			R-HSA-912429 (Reactome)	Meiotic Holliday junctions are cleaved to yield either crossovers or non?crossovers (gene conversions). The resolvase or resolvases responsible for cleavage are unknown but a resolvase complex may include SLX4 and/or GEN1. Two classes of crossovers have been defined: class I crossovers are dependent on the MutL homologs, MLH1 and MLH3, while class II crossovers are dependent on the MUS81-EME1 endonuclease. Class I crossovers constitute 90-95% of all crossovers, and correspond to meiotic nodules that contain MLH1and MLH3. These arise as a subset of the many hundreds of MSH4/MSH5-positive meiotic nodules that arise at the time of double Holliday junction formation. What happens to all the other meiotic nodules is not clear, but they most likely follow a second pathway that results in non-crossovers (or gene conversions). MLH1 and MLH3 form heterodimers that repair mismatches in duplex DNA. In mouse, MLH1 is required for crossovers but not for non?crossover resolution of Holliday junctions. About 10% of early meiotic nodules are somehow selected to become Class I crossover events, possibly by first losing BLM (and probably associated TOP3A), and acquiring MLH1 and MLH3. The selection of sites for class II crossovers follows an, as yet, unknown pathway, but almost certainly stems from the same initiating D-loop intermediate. In the process known as crossover interference, the presence of a crossover nodule inhibits formation of nearby crossover nodules so that crossovers are not clustered and each chromosome bivalent has at least one crossover. In mouse, crossover interference is seen among nodules at two stages: RPA?containing nodules during late zygonema and MLH1?containing nodules during pachynema. Class II crossovers are not subject to interference constraints.
			R-HSA-912458 (Reactome)	Following double strand break (DSB) formation and strand resection, RAD51 and DMC1 coat single-stranded 3' ends of DNA and catalyze the search for homology and strand invasion into the DNA duplex of the chromosomal homolog (Baumann et al. 1996, Barlow et al. 1997, Benson et al. 1998, Baumann and West 1999, Masson et al. 1999, Sehorn et al. 2004, Murayama et al. 2008). The invading strand displaces the original strand of the chromosomal homolog creating a D-loop structure. Other proteins present in the complex are inferred from cytology (Barlow et al. 1997, Oliver-Bonet et al. 2005, Oliver-Bonet et al. 2007).
			R-HSA-912496 (Reactome)	The 3' end of the invading strand is extended by an unknown DNA polymerase and the extended strand is then ligated back to the original homolog, generating a double Holliday junction. MSH4 and MSH5 form heterodimers which bind Holliday junctions and, in the presence of ATP, slide along the parental duplexes (Bocker et al. 1999, Snowden et al. 2004, Snowden et al. 2008). MSH4 is present at hundreds of meiotic nodules during late zygotene but only about 10% of these nodules become crossovers (Oliver-Bonet et al. 2005). Bloom Syndrome protein (BLM) and Topoisomerase IIIa (TOP3A) are also present and may promote homologous recombination repair without crossing over (Johnson et al. 2000, Wu et al. 2000).
			R-HSA-912503 (Reactome)	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.
	RAD51	Arrow	R-HSA-912496 (Reactome)
RAD51C		Arrow	R-HSA-912503 (Reactome)
RAD51			R-HSA-912503 (Reactome)
	RPA heterotrimer	Arrow	R-HSA-912429 (Reactome)
RPA heterotrimer			R-HSA-912503 (Reactome)
SPO11 Dimer			R-HSA-912368 (Reactome)
SPO11 Dimer		mim-catalysis	R-HSA-912368 (Reactome)
	SPO11:double stand break	Arrow	R-HSA-912368 (Reactome)
SPO11:double stand break			R-HSA-912397 (Reactome)
	SPO11:oligonucleotide	Arrow	R-HSA-912397 (Reactome)
TEX15		Arrow	R-HSA-912503 (Reactome)
	TOP3A	Arrow	R-HSA-912429 (Reactome)
TOP3A			R-HSA-912496 (Reactome)