Crossover junction endonuclease MUS81 is anenzyme that in humans is encoded by theMUS81gene.[5][6][7]
In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4), play overlapping and essential roles in completion of homologous recombination.[8] The significant overlap in function between these enzymes is most likely related to processing joint molecules such asD-loops and nickedHolliday junctions.[8]
MUS81 is a component of a minorchromosomal crossover (CO) pathway in themeiosis ofbudding yeast, plants and vertebrates.[9] However, in the protozoanTetrahymena thermophila, MUS81 appears to be part of an essential (if not the predominant) CO pathway.[9] The MUS81 pathway also appears to be the predominant CO pathway in the fission yeastSchizosaccharomyces pombe.[9]
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.
The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram.Recombination duringmeiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process calledresection. In thestrand invasion step that follows, an overhanging 3' end of the broken DNA molecule "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways, leading to a crossover (CO) or a non-crossover (NCO) recombinant (seeGenetic recombination). The pathway leading to a CO involves a doubleHolliday junction (DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed.
MUS81-MMS4, in the budding yeastSaccharomyces cerevisiae, is a DNA structure-selectiveendonuclease that cleaves joint DNA molecules formed duringhomologous recombination inmeiosis andmitosis.[10] The MUS81-MMS4 endonuclease, although a minor resolvase for CO formation inS. cerevisiae, is crucial for limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from the same DSB.[11]
Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs.[12]
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