Editing Chromosomal crossover (section)

===Class I and class II crossovers===
Double-strand breaks are repaired by two pathways to generate crossovers in eukaryotes.<ref>{{cite journal | vauthors = Holloway JK, Booth J, Edelmann W, McGowan CH, Cohen PE | title = MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis | journal = PLOS Genetics | volume = 4 | issue = 9 | pages = e1000186 | date = September 2008 | pmid = 18787696 | pmc = 2525838 | doi = 10.1371/journal.pgen.1000186 | doi-access = free }}</ref> The majority of them are repaired by MutL homologs MLH1 and MLH3, which defines the class I crossovers. The remaining are the result of the class II pathway, which is regulated by MUS81 endonuclease and [[FANCM]] translocase. There are interconnections between these two pathways—class I crossovers can compensate for the loss of class II pathway. In MUS81 knockout mice, class I crossovers are elevated, while total crossover counts at chiasmata are normal. However, the mechanisms underlining this crosstalk are not well understood. A recent study suggests that a scaffold protein called SLX4 may participate in this regulation.<ref>{{cite journal | vauthors = Holloway JK, Mohan S, Balmus G, Sun X, Modzelewski A, Borst PL, Freire R, Weiss RS, Cohen PE | display-authors = 6 | title = Mammalian BTBD12 (SLX4) protects against genomic instability during mammalian spermatogenesis | journal = PLOS Genetics | volume = 7 | issue = 6 | pages = e1002094 | date = June 2011 | pmid = 21655083 | pmc = 3107204 | doi = 10.1371/journal.pgen.1002094 | doi-access = free }}</ref> Specifically, SLX4 knockout mice largely phenocopies the MUS81 knockout—once again, an elevated class I crossovers while normal chiasmata count. In FANCM knockout mice, the class II pathway is hyperactivated, resulting in increased numbers of crossovers that are independent of the MLH1/MLH3 pathway.<ref>{{cite journal | vauthors = Tsui V, Lyu R, Novakovic S, Stringer JM, Dunleavy JE, Granger E, Semple T, Leichter A, Martelotto LG, Merriner DJ, Liu R, McNeill L, Zerafa N, Hoffmann ER, O'Bryan MK, Hutt K, Deans AJ, Heierhorst J, McCarthy DJ, Crismani W | display-authors = 6 | title = ''Fancm'' has dual roles in the limiting of meiotic crossovers and germ cell maintenance in mammals | journal = Cell Genomics | volume = 3 | issue = 8 | pages = 100349 | date = August 2023 | pmid = 37601968 | pmc = 10435384 | doi = 10.1016/j.xgen.2023.100349 }}</ref>