DNA replication licensing factor MCM6 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''MCM6''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. MCM6 is one of the highly conserved mini-chromosome maintenance proteins ( MCM) that are essential for the initiation of

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

replication.

Function

The MCM complex consisting of MCM6 (this protein) and

MCM2 DNA replication licensing factor MCM2 is a protein that in humans is encoded by the ''MCM2'' gene. Function The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the in ...

, 4 and 7 possesses DNA

helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...

activity, and may act as a DNA unwinding

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

. The hexameric protein complex formed by the MCM proteins is a key component of the

pre-replication complex A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of ...

(pre-RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Mcm 6 has recently been shown to interact strongly

Cdt1 CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the ''CDT1'' gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle. Role in pre-replication co ...

at defined residues, by mutating these target residues Wei ''et al''. observed lack of Cdt1 recruitment of Mcm2-7 to the pre-RC.

Gene

The MCM6 gene, ''MCM6'', is expressed at very high level. ''MCM6'' contains 18

intron An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of ...

s. There are 2 non overlapping alternative last

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s. 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 Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be i ...

, 3 different transcripts, all with introns, putatively encoding 3 different protein

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some is ...

s. ''MCM6'' contains two of the regulatory regions for ''LCT'', the gene encoding the protein

lactase Lactase is an enzyme produced by many organisms. It is located in the brush border of the small intestine of humans and other mammals. Lactase is essential to the complete digestion of whole milk; it breaks down lactose, a sugar which gives ...

, located in two of the ''MCM6'' introns, approximately 14 kb (-13910) and 22 kb (-22018) upstream of ''LCT''. The (-13910) region, in particular, has been shown to function ''in vitro'' as an enhancer element capable of differentially activating transcription of ''LCT'' promoter.

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s in these regions are associated with

lactose tolerance Lactase persistence is the continued activity of the lactase enzyme in adulthood, allowing the digestion of lactose in milk. In most mammals, the activity of the enzyme is dramatically reduced after weaning. In some human populations, though, lact ...

into adult life. " Two variants were associated with lactase persistence..."

Interactions

MCM6 has been shown to

interact Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...

with: *

CDC45-related protein CDC45 is a protein that in humans is encoded by the ''CDC45L'' gene. Function The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA ...

, *

MCM4 DNA replication licensing factor MCM4 is a protein that in humans is encoded by the ''MCM4'' gene. Function The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the i ...

, *

MCM7 DNA replication licensing factor MCM7 is a protein that in humans is encoded by the ''MCM7'' gene. Function The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the in ...

, *

ORC1L Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea. Function The origin recognition complex (ORC) is a highly conserved six sub ...

, *

ORC2L Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans. Function The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA rep ...

, * ORC4L, and * Replication protein A1.

Function

Gene

Interactions

See also

References

Further reading