MCM6

MCM6

MCM6, or minichromosome maintenance deficient 6 gene is one of the highly conserved MCMs that are essential for the initiation of eukaryotic genome replication. The MCM complex consisting of this protein and MCM2, 4 and 7 possesses DNA helicase activity, and may act as a DNA unwinding enzyme. PBB_Summary
section_title =
summary_text = The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication.cite web | title = Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4175| accessdate = ]

Gene

The MCM6 gene, "MCM6", is expressed at very high level. "MCM6" contains 18 introns. There are 2 non overlapping alternative last exons. The transcripts appear to differ by truncation of the 3' end, presence or absence of 2 cassette exons, common exons with different boundaries.

"MCM6" produces, by alternative splicing, 3 different transcripts, all with introns, putatively encoding 3 different protein isoforms.

"MCM6" contains two of the regulatory reagons for "LCT". They are located in two of the "MCM6" intrones, approximately 14 kb (-13910) and 22 kb (-22018) upstream of "LCT" Identification of a variant associated with adult-type hypolactasia "Nat Genet. 2002 Feb; 30(2): 233-7" [http://www.nature.com/ng/journal/v30/n2/full/ng826.html Free text] ] . One of them, the (-13910) region, has been shown to function "in vitro" as a "cis" element capable of enhancing differential transcriptional activation of "LCT" promoter [Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. "Hum Mol Genet. 2003 Sep 15; 12(18): 2333-40." [http://hmg.oxfordjournals.org/cgi/content/full/12/18/2333 Free text] ] . Mutations in these regions are associated with lactose tolerance into adult life.

ee also

*Mini Chromosome Maintenance

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Ishimi Y, Ichinose S, Omori A, "et al." |title=Binding of human minichromosome maintenance proteins with histone H3. |journal=J. Biol. Chem. |volume=271 |issue= 39 |pages= 24115–22 |year= 1996 |pmid= 8798650 |doi=
*cite journal | author=Holthoff HP, Hameister H, Knippers R |title=A novel human Mcm protein: homology to the yeast replication protein Mis5 and chromosomal location. |journal=Genomics |volume=37 |issue= 1 |pages= 131–4 |year= 1997 |pmid= 8921380 |doi= 10.1006/geno.1996.0530
*cite journal | author=Harvey CB, Wang Y, Darmoul D, "et al." |title=Characterisation of a human homologue of a yeast cell division cycle gene, MCM6, located adjacent to the 5' end of the lactase gene on chromosome 2q21. |journal=FEBS Lett. |volume=398 |issue= 2-3 |pages= 135–40 |year= 1997 |pmid= 8977093 |doi=
*cite journal | author=Tsuruga H, Yabuta N, Hosoya S, "et al." |title=HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5. |journal=Genes Cells |volume=2 |issue= 6 |pages= 381–99 |year= 1997 |pmid= 9286856 |doi=
*cite journal | author=Ishimi Y |title=A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex. |journal=J. Biol. Chem. |volume=272 |issue= 39 |pages= 24508–13 |year= 1997 |pmid= 9305914 |doi=
*cite journal | author=Holthoff HP, Baack M, Richter A, "et al." |title=Human protein MCM6 on HeLa cell chromatin. |journal=J. Biol. Chem. |volume=273 |issue= 13 |pages= 7320–5 |year= 1998 |pmid= 9516426 |doi=
*cite journal | author=Ohtani K, Iwanaga R, Nakamura M, "et al." |title=Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. |journal=Oncogene |volume=18 |issue= 14 |pages= 2299–309 |year= 1999 |pmid= 10327050 |doi= 10.1038/sj.onc.1202544
*cite journal | author=You Z, Komamura Y, Ishimi Y |title=Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity. |journal=Mol. Cell. Biol. |volume=19 |issue= 12 |pages= 8003–15 |year= 2000 |pmid= 10567526 |doi=
*cite journal | author=Ishimi Y, Komamura-Kohno Y, You Z, "et al." |title=Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2. |journal=J. Biol. Chem. |volume=275 |issue= 21 |pages= 16235–41 |year= 2000 |pmid= 10748114 |doi= 10.1074/jbc.M909040199
*cite journal | author=Izumi M, Yanagi K, Mizuno T, "et al." |title=The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase. |journal=Nucleic Acids Res. |volume=28 |issue= 23 |pages= 4769–77 |year= 2001 |pmid= 11095689 |doi=
*cite journal | author=Lee JK, Hurwitz J |title=Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=98 |issue= 1 |pages= 54–9 |year= 2001 |pmid= 11136247 |doi= 10.1073/pnas.98.1.54
*cite journal | author=Enattah NS, Sahi T, Savilahti E, "et al." |title=Identification of a variant associated with adult-type hypolactasia. |journal=Nat. Genet. |volume=30 |issue= 2 |pages= 233–7 |year= 2002 |pmid= 11788828 |doi= 10.1038/ng826
*cite journal | author=Yanagi K, Mizuno T, You Z, Hanaoka F |title=Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. |journal=J. Biol. Chem. |volume=277 |issue= 43 |pages= 40871–80 |year= 2002 |pmid= 12192004 |doi= 10.1074/jbc.M206202200
*cite journal | author=You Z, Ishimi Y, Masai H, Hanaoka F |title=Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex. |journal=J. Biol. Chem. |volume=277 |issue= 45 |pages= 42471–9 |year= 2003 |pmid= 12207017 |doi= 10.1074/jbc.M205769200
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Kneissl M, Pütter V, Szalay AA, Grummt F |title=Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells. |journal=J. Mol. Biol. |volume=327 |issue= 1 |pages= 111–28 |year= 2003 |pmid= 12614612 |doi=
*cite journal | author=Yabuta N, Kajimura N, Mayanagi K, "et al." |title=Mammalian Mcm2/4/6/7 complex forms a toroidal structure. |journal=Genes Cells |volume=8 |issue= 5 |pages= 413–21 |year= 2004 |pmid= 12694531 |doi=
*cite journal | author=Johnson EM, Kinoshita Y, Daniel DC |title=A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13. |journal=Nucleic Acids Res. |volume=31 |issue= 11 |pages= 2915–25 |year= 2003 |pmid= 12771218 |doi=
*cite journal | author=Ramachandran N, Hainsworth E, Bhullar B, "et al." |title=Self-assembling protein microarrays. |journal=Science |volume=305 |issue= 5680 |pages= 86–90 |year= 2004 |pmid= 15232106 |doi= 10.1126/science.1097639
*cite journal | author=Yu Z, Feng D, Liang C |title=Pairwise interactions of the six human MCM protein subunits. |journal=J. Mol. Biol. |volume=340 |issue= 5 |pages= 1197–206 |year= 2004 |pmid= 15236977 |doi= 10.1016/j.jmb.2004.05.024

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