DMC1 (gene)

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DNA meiotic recombinase 1
Protein DMC1 PDB 1v5w.png
PDB rendering based on 1v5w.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DMC1 ; DMC1H; LIM15; dJ199H16.1
External IDs OMIM602721 MGI105393 HomoloGene5135 GeneCards: DMC1 Gene
RNA expression pattern
PBB GE DMC1 208382 s at tn.png
PBB GE DMC1 208386 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 11144 13404
Ensembl ENSG00000100206 ENSMUSG00000022429
UniProt Q14565 Q61880
RefSeq (mRNA) NM_001278208 NM_001278226
RefSeq (protein) NP_001265137 NP_001265155
Location (UCSC) Chr 22:
38.52 – 38.57 Mb
Chr 15:
79.56 – 79.61 Mb
PubMed search [1] [2]

Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the DMC1 gene.[1][2][3][4]

Meiotic recombination protein Dmc1 is a homolog of the bacterial strand exchange protein RecA. Dmc1 plays the central role in homologous recombination in meiosis by assembling at the sites of programmed DNA double strand breaks and carrying out a search for allelic DNA sequences located on homologous chromatids. The name "Dmc" stands for "disrupted meiotic cDNA" and refers to the method used for its discovery which involved using clones from a meiosis-specific cDNA library to direct knock-out mutations of abundantly expressed meiotic genes. The Dmc1 protein is one of two homologs of RecA found in eukaryotic cells, the other being Rad51. In budding yeast, Rad51 serves as a strand exchange protein in mitosis where it is critical for the repair of DNA breaks. Rad51 is converted to an accessory factor for Dmc1 during meiosis by inhibition of its strand exchange activity.[5] Homologs of DMC1 have been identified in many organisms including divergent fungi, plants and mammals including humans.[1][2][3][4]

Discovery[edit]

The DMC1 gene and protein were discovered in the budding yeast S. cerevisiae by Douglas Bishop when he was a postdoctoral fellow in the laboratory of Nancy Kleckner at Harvard University.[6]

Function[edit]

The protein encoded by this gene is essential for meiotic homologous recombination. Genetic recombination in meiosis plays an important role in generating diversity of genetic information and is essential for the reductional segregation of chromosomes that must occur for formation of gametes during sexual reproduction.

Like other members of the Rad51/RecA family, Dmc1 stabilizes strand exchange intermediates (Rad1/RecA-stretched DNA, or RS-DNA) in stretched triplets similar to B form DNA. Each molecule of the protein binds a triplet of nucleotides, and the strength of that binding, as assessed by the change in Gibbs free energy, can be assessed by the length of time that a labelled dsDNA probe with a short homologous sequence remains bound to a DNA containing a short region of homology to it. A study of this type has shown that a mismatch in any of the three positions at the end of a stretch of homology will not increase the length of time that the probe remains bound, and in Rad51 or RecA constructs an internal mismatch will cause a similar reduction in binding time. All of the enzymes are capable of "stepping over" a mismatch and continuing to bind the probe more firmly if a longer region of homology exists. However, with Dmc1 a triplet with a single internal (but not terminal) mismatch will contribute to the stability of probe binding to a similar extent as one without a mismatch. In this way, Dmc1 is specially suited to its role as a meiosis-specific recombinase, as this activity permits it more effectively to catalyze recombination between sequences that are not perfectly matched.[7]

Interactions[edit]

DMC1 (gene) has been shown to interact with RAD51.[8] The protein has also been shown to bind Tid1(Rdh54), Mei5/Sae3, and Hop2/Mnd1. All of these interacting proteins act to enhance Dmc1's activity in purified systems and are also implicated as being required for Dmc1 function in cells.

References[edit]

  1. ^ a b Habu T, Taki T, West A, Nishimune Y, Morita T (1996). "The mouse and human homologs of DMC1, the yeast meiosis-specific homologous recombination gene, have a common unique form of exon-skipped transcript in meiosis". Nucleic Acids Res. 24 (3): 470–7. doi:10.1093/nar/24.3.470. PMC 145652. PMID 8602360. 
  2. ^ a b Sato S, Seki N, Hotta Y, Tabata S (1995). "Expression profiles of a human gene identified as a structural homologue of meiosis-specific recA-like genes". DNA Res. 2 (4): 183–6. doi:10.1093/dnares/2.4.183. PMID 8590282. 
  3. ^ a b Thorslund T, Esashi F, West SC (2007). "Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1". EMBO J. 26 (12): 2915–22. doi:10.1038/sj.emboj.7601739. PMC 1894777. PMID 17541404. 
  4. ^ a b "Entrez Gene: DMC1 DMC1 dosage suppressor of mck1 homolog, meiosis-specific homologous recombination (yeast)". 
  5. ^ Cloud V, Chan YL, Grubb J, Budke B, Bishop DK (2012). "Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis". Science 337 (6099): 1222–5. doi:10.1126/science.1219379. PMID 22955832. 
  6. ^ Bishop DK, Park D, Xu L, Kleckner N (1992). "DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression". Cell 69 (3): 439–56. doi:10.1016/0092-8674(92)90446-j. PMID 1581960. 
  7. ^ Lee JY, Terakawa T, Qi Z, Steinfeld JB, Redding S, Kwon Y, Gaines WA, Zhao W, Sung P, Greene EC (Aug 2015). "DNA recombination. Base triplet stepping by the Rad51/RecA family of recombinases". Science 349 (6251): 977–81. doi:10.1126/science.aab2666. PMID 26315438. 
  8. ^ Masson JY, Davies AA, Hajibagheri N, Van Dyck E, Benson FE, Stasiak AZ, Stasiak A, West SC (Nov 1999). "The meiosis-specific recombinase hDmc1 forms ring structures and interacts with hRad51". EMBO J. 18 (22): 6552–60. doi:10.1093/emboj/18.22.6552. PMC 1171718. PMID 10562567. 

Further reading[edit]