Catalysis of the reaction: ATP + H2O = ADP + phosphate; this reaction requires the presence of single- or double-stranded DNA, and it drives another reaction.
The cell cycle process in which a connection between chromatids assembles, indicating where an exchange of homologous segments has taken place by the crossing-over of non-sister chromatids.
The cell cycle process in which replicated homologous chromosomes are organized and then physically separated and apportioned to two sets during the first division of the meiotic cell cycle. Each replicated chromosome, composed of two sister chromatids, aligns at the cell equator, paired with its homologous partner; this pairing off, referred to as synapsis, permits genetic recombination. One homolog (both sister chromatids) of each morphologic type goes into each of the resulting chromosome sets.
A cell cycle process comprising the steps by which a cell progresses through the nuclear division phase of a meiotic cell cycle. A meiotic cell cycle is the specialized nuclear and cell division in which a single diploid cell undergoes two nuclear divisions following a single round of DNA replication in order to produce four daughter cells that contain half the number of chromosomes as the diploid cell. Meiotic division occurs during the formation of gametes from diploid organisms and at the beginning of haplophase in those organisms that alternate between diploid and haploid generations.
We have cloned and characterized the human orthologue of the Saccharomyces cerevisiae MutS homologue 5 (MSH5) cDNA, as well as the human gene that encodes the MSH5 cDNA, as a step toward understanding the molecular genetic mechanisms involved in the biological function of this novel human protein. The identified cDNA contains a 2505-bp open reading frame (ORF) that encodes an 834-amino-acid polypeptide with a predicted molecular mass of 92.9 kDa. The amino acid sequence encoded by this cDNA includes sequence motifs that are conserved in all known MutS homologues existing in bacteria to humans. The cDNA appears, on the basis of amino acid sequence analysis, to be a member of the MutS family and shares 30% sequence identity with that of S. cerevisiae MSH5, a yeast gene that plays a critical role in facilitating crossover during meiosis. Northern blot analysis demonstrated the presence of a 2.9-kb human MSH5 mRNA species in all human tissues tested, but the highest expression was in human testis, an organ containing cells that undergo constant DNA synthesis and meiosis. The expression pattern of human MSH5 resembled that of the previously identified human MutS homologues MSH2, MSH3, and MSH6-genes that are involved in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to expedite the search for potential disease association with this new human MutS homologue, we have also determined the chromosomal location and structure of the human MSH5 locus. Sequence and structural characterization demonstrated that MSH5 spans approximately 25 kb and contains 26 exons that range in length from 36 bp for exon 8 to 254 bp for exon 25. MSH5 has been mapped to human chromosome band 6p21.3 by fluorescence in situ hybridization. Knowledge of the sequence and gene structure of MSH5 will now enable studies of the possible roles MSH5 may play in meiosis and/or DNA replicative mismatch repair.
A system for the identification and correction of base-base mismatches, small insertion-deletion loops, and regions of heterology that are present in duplex DNA formed with strands from two recombining molecules. Correction of the mismatch can result in non-Mendelian segregation of alleles following meiosis.
Prophase occurring as part of meiosis II. Prophase is the part of nuclear division in which, canonically, chromosomes condense and the two daughter centrioles and their asters migrate toward the poles of the cell. Meiosis II is the second phase of meiosis, in which cells divide and separate the two chromatids in each chromosome.
MSH5 (MutS homologue 5) is a member of a family of proteins known to be involved in DNA mismatch repair. Germline mutations in MSH2, MLH1 and GTBP (also known as MSH6) cause hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome. Inactivation of Msh2, Mlh1, Gtmbp (also known as Msh6) or Pms2 in mice leads to hereditary predisposition to intestinal and other cancers. Early studies in yeast revealed a role for some of these proteins, including Msh5, in meiosis. Gene targeting studies in mice confirmed roles for Mlh1 and Pms2 in mammalian meiosis. To assess the role of Msh5 in mammals, we generated and characterized mice with a null mutation in Msh5. Msh5-/- mice are viable but sterile. Meiosis in these mice is affected due to the disruption of chromosome pairing in prophase I. We found that this meiotic failure leads to a diminution in testicular size and a complete loss of ovarian structures. Our results show that normal Msh5 function is essential for meiotic progression and, in females, gonadal maintenance.
A system for the correction of errors in which an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. The mismatch repair system promotes genomic fidelity by repairing base-base mismatches, insertion-deletion loops and heterologies generated during DNA replication and recombination.
We have cloned and characterized the human orthologue of the Saccharomyces cerevisiae MutS homologue 5 (MSH5) cDNA, as well as the human gene that encodes the MSH5 cDNA, as a step toward understanding the molecular genetic mechanisms involved in the biological function of this novel human protein. The identified cDNA contains a 2505-bp open reading frame (ORF) that encodes an 834-amino-acid polypeptide with a predicted molecular mass of 92.9 kDa. The amino acid sequence encoded by this cDNA includes sequence motifs that are conserved in all known MutS homologues existing in bacteria to humans. The cDNA appears, on the basis of amino acid sequence analysis, to be a member of the MutS family and shares 30% sequence identity with that of S. cerevisiae MSH5, a yeast gene that plays a critical role in facilitating crossover during meiosis. Northern blot analysis demonstrated the presence of a 2.9-kb human MSH5 mRNA species in all human tissues tested, but the highest expression was in human testis, an organ containing cells that undergo constant DNA synthesis and meiosis. The expression pattern of human MSH5 resembled that of the previously identified human MutS homologues MSH2, MSH3, and MSH6-genes that are involved in the pathogenesis of hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to expedite the search for potential disease association with this new human MutS homologue, we have also determined the chromosomal location and structure of the human MSH5 locus. Sequence and structural characterization demonstrated that MSH5 spans approximately 25 kb and contains 26 exons that range in length from 36 bp for exon 8 to 254 bp for exon 25. MSH5 has been mapped to human chromosome band 6p21.3 by fluorescence in situ hybridization. Knowledge of the sequence and gene structure of MSH5 will now enable studies of the possible roles MSH5 may play in meiosis and/or DNA replicative mismatch repair.
The cell cycle process in which double strand breaks are formed and repaired through a double Holliday junction intermediate. This results in the equal exchange of genetic material between non-sister chromatids in a pair of homologous chromosomes. These reciprocal recombinant products ensure the proper segregation of homologous chromosomes during meiosis I and create genetic diversity.
IBARefGenome
Pathways
According to Reactome, this protein belongs to the following pathway:
Protein involved in meiotic processes or in regulation of meiosis. Meiosis is the nuclear division which results in the daughter nuclei each containing half the number of chromosomes of the parent. It comprises two distinct nuclear divisions, the first and second meiotic divisions (which may be separated by cell division), the actual reduction in chromosome number takes place during the first division.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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