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Crossover junction endonuclease MUS81 is an
The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram. Recombination during
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''MUS81'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4
ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ''ERCC4'' gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and Genetic recombination, DNA recombinat ...
), play overlapping and essential roles in completion of homologous recombination. The significant overlap in function between these enzymes is most likely related to processing joint molecules such as D-loop
In molecular biology, a displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA. An R-loop is similar to a D-loop, but in that cas ...
s and nicked Holliday junctions.
Meiosis
MUS81 is a component of a minorchromosomal crossover
Chromosomal crossover, or crossing over, is the exchange of genetic material during sexual reproduction between two homologous chromosomes' sister chromatids, non-sister chromatids that results in recombinant chromosomes. It is one of the fina ...
(CO) pathway in the meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
of budding yeast
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been ...
, plants and vertebrates. However, in the protozoan ''Tetrahymena
''Tetrahymena'' is a genus of free-living ciliates, examples of unicellular eukaryotes. The genus Tetrahymena is the most widely studied member of its phylum. It can produce, store and react with different types of hormones. ''Tetrahymena'' cel ...
thermophila'', MUS81 appears to be part of an essential (if not the predominant) CO pathway. The MUS81 pathway also appears to be the predominant CO pathway in the fission yeast ''Schizosaccharomyces pombe
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
''.
The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram. Recombination during meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
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 called ''resection''. In the ''strand 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
In molecular biology, a displacement loop or D-loop is a DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA. An R-loop is similar to a D-loop, but in that cas ...
). 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 (see Genetic recombination
Genetic recombination (also known as genetic reshuffling) is the exchange of genetic material between different organisms which leads to production of offspring with combinations of traits that differ from those found in either parent. In eukaryot ...
). The pathway leading to a CO involves a double Holliday junction
A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the j ...
(DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed.
MUS81-MMS4, in the budding yeast ''Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...
'', is a DNA structure-selective endonuclease
In molecular biology, endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain (namely DNA or RNA). Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (with regard to sequence), while man ...
that cleaves joint DNA molecules formed during homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
in meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
and mitosis
Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
. The MUS81-MMS4 endonuclease, although a minor resolvase for CO formation in ''S. cerevisiae'', is crucial for limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from the same DSB.
Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs.
Interactions
MUS81 has been shown to interact withCHEK2
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been link ...
.
References
Further reading
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