Holliday junction: Difference between revisions

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===Resolution===
In budding yeast ''[[Saccharomyces cerevisiae]]'', Holliday junctions can be resolved by four different pathways that account for essentially all Holliday junction resolution [[in vivo]].<ref name=Zakh>{{cite journal | last1 = Zakharyevich | first1 = K | last2 = Tang | first2 = S | last3 = Ma | first3 = Y | last4 = Hunter | first4 = N | date = April 2012 | title = Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase | url = | journal = Cell. | volume = 149 | issue = 2| pages = 334–47 | doi = 10.1016/j.cell.2012.03.023 | pmid = 22500800 | pmc=3377385}}</ref> The pathway that produces the majority of [[Chromosomal crossover|crossovers]] in ''S. cerevisiae'' budding yeast, and possibly in mammals, involves proteins [[Exonuclease 1|EXO1]], [[MLH1]]-[[MLH3]] heterodimer (called MutL gamma) and [[Sgs1|SGS1]] (ortholog of [[Bloom syndrome protein|Bloom syndrome helicase]]).<ref name=Zakh /> The MLH1-MLH3 heterodimer binds preferentially to Holliday junctions.<ref name=Ranjha>Ranjha L, Anand R, Cejka P. 2014. The Saccharomyces cerevisiae Mlh1-Mlh3 heterodimer is an endonuclease that preferentially binds to Holliday junctions. J Biol Chem. 2014 Feb 28;289(9):5674-86. doi: 10.1074/jbc.M113.533810. {{PMID |24443562}}</ref> It is an endonuclease that makes single-strand breaks in supercoiled double-stranded DNA.<ref name=Ranjha /><ref name="pmid24403070">{{vcite2 journal |vauthors=Rogacheva MV, Manhart CM, Chen C, Guarne A, Surtees J, Alani E |title=Mlh1-Mlh3, a meiotic crossover and DNA mismatch repair factor, is a Msh2-Msh3-stimulated endonuclease |journal=J. Biol. Chem. |volume=289 |issue=9 |pages=5664–73 |year=2014 |pmid=24403070 |pmc=3937641 |doi=10.1074/jbc.M113.534644 |url=}}</ref> The MLH1-MLH3 heterodimer promotes the formation of [[Chromosomal crossover|crossover recombinants]].<ref name=Brown>{{vcite2 journal |vauthors=Sonntag Brown M, Lim E, Chen C, Nishant KT, Alani E |title=Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast |journal=G3: Genes, Genomes, Genetics |volume=3 |issue=1 |pages=9–22 |year=2013 |pmid=23316435 |pmc=3538346 |doi=10.1534/g3.112.004622 |url=}}</ref> While the other three pathways, involving proteins [[MUS81]]-MMS4, SLX1 and YEN1, respectively, can promote Holliday junction resolution in vivo, absence of all three nucleases has only a modest impact on formation of crossover products.
 
Double mutants deleted for both MLH3 (major pathway) and MMS4 (minor pathway) showed dramatically reduced crossing over compared to wild-type (6- to 17-fold); however spore viability was reasonably high (62%) and chromosomal disjunction appeared mostly functional.<ref name=Brown />