Resolution of meiotic holliday junction

Stable Identifier
R-HSA-912429
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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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.

Literature References
PubMed ID Title Journal Year
16322221 Expression of the MutL homologue hMLH3 in human cells and its role in DNA mismatch repair

Cannavo, E, Marra, G, Sabates-Bellver, J, Menigatti, M, Lipkin, SM, Fischer, F, Cejka, P, Jiricny, J

Cancer Res 2005
16123081 Temporal progression of recombination in human males

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

Mol Hum Reprod 2005
11292842 The interacting domains of three MutL heterodimers in man: hMLH1 interacts with 36 homologous amino acid residues within hMLH3, hPMS1 and hPMS2

Kondo, E, Horii, A, Fukushige, S

Nucleic Acids Res 2001
9781043 Crossing over analysis at pachytene in man

Barlow, AL, Hultén, MA

Eur J Hum Genet 1998
10928988 MSH4 acts in conjunction with MLH1 during mammalian meiosis

Santucci-Darmanin, S, Walpita, D, Lespinasse, F, Desnuelle, C, Ashley, T, Paquis-Flucklinger, V

FASEB J 2000
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