MCM4/YPR019W Summary Help

Standard Name MCM4 1
Systematic Name YPR019W
Alias HCD21 2 , CDC54 3
Feature Type ORF, Verified
Description Essential helicase component of heterohexameric MCM2-7 complexes; MCM2-7 complexes bind pre-replication complexes on DNA and melt DNA prior to replication; forms an Mcm4p-6p-7p subcomplex; shows nuclear accumulation in G1; homolog of S. pombe Cdc21p (4, 5, 6, 7 and see Summary Paragraph)
Name Description MiniChromosome Maintenance 1
Chromosomal Location
ChrXVI:596750 to 599551 | ORF Map | GBrowse
Gene Ontology Annotations All MCM4 GO evidence and references
  View Computational GO annotations for MCM4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Classical genetics
reduction of function
Large-scale survey
211 total interaction(s) for 69 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 43
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 68
  • Biochemical Activity: 10
  • Co-crystal Structure: 1
  • Co-fractionation: 3
  • Co-localization: 7
  • Co-purification: 9
  • Reconstituted Complex: 26
  • Two-hybrid: 9

Genetic Interactions
  • Dosage Growth Defect: 5
  • Dosage Lethality: 1
  • Phenotypic Enhancement: 5
  • Phenotypic Suppression: 1
  • Synthetic Growth Defect: 11
  • Synthetic Lethality: 10
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 933
Molecular Weight (Da) 105,002
Isoelectric Point (pI) 6.13
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXVI:596750 to 599551 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2802 596750..599551 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000006223

The Mcm2-7 family is a group of six proteins that are highly conserved in all eukaryotes, with homologs having also been identified in Archaea (reviewed in 4 and 8). They are required for cell cycle progression and DNA replication initiation and elongation. Three of the genes (MCM4/CDC54, MCM5/CDC46, MCM7/CDC47) were originally identified as Cell Division Cycle mutants (9, 3). In S. cerevisiae, each of the six Mcm2-7 proteins (encoded by MCM2, MCM3, MCM4/CDC54, MCM5/CDC46, MCM6, and MCM7/CDC47) is essential for viability (10, 8, 3, 11).

Mcm2-7p (MiniChromosome Maintenance) form a ring-shaped heterohexamer (MCM complex) that binds chromosomal replication origins and assembles as part of the prereplicative complex (pre-RC) during the G1 phase of the cell cycle (12, 13, 14, 15). Other components of the pre-RC include the origin recognition complex (ORC; Orc1-6p), Cdc6p, and Tah11p (aka Cdt1p) (13). ORC activation of the origin DNA leads to the binding of the MCM proteins to the unwound origin (15). At the G1-S transition, ORC and the MCM proteins are phosphorylated by S-phase-specific cyclin-dependent kinases (Cdks) which transform the pre-RC into an active replication complex. The MCM complex translocates along the DNA with the replication fork during S phase (16). Other S- and M-phase Cdks block the rebinding of MCMs to origin chromatin and prevent reinitiation of replication until mitosis is complete (15).

Mcm2-7p undergo cell cycle-regulated cellular localization, accumulating in the nucleus during G1, only to be excluded from the nucleus later in the cell cycle (16, 17, 18, 19). Tah11p exhibits this same cell cycle-regulated cellular localization pattern, and the nuclear accumulation of these proteins during G1 is interdependent. The MCM complex appears to interact with Tah11p prior to binding replication origin chromatin during pre-RC assembly (13).

Each MCM protein is a member of the AAA+ class of ATPases and has an ATP binding site, although no individual MCM protein alone contains significant ATPase activity (15, 14). ATPase activity is produced only by a combination of at least two MCM proteins, requiring a catalytic residue from one subunit and an ATP binding site from another, consistent with the location of ATP sites at the interfaces of AAA+ protein complexes (14). Pairwise studies of the six subunits have revealed ATPase activity in only three pairs: Mcm2/6p, Mcm4/7p, and Mcm3/7p (14). The majority of ATPase activity, however, is produced by the MCM complex as a whole (14). DNA helicase activity is associated only with Mcm4p, Mcm6p, and Mcm7p, which can also form a doughnut-shaped heterohexamer. This replicative DNA helicase complex (Mcm467) binds the leading strand and unwinds DNA in an ATP-dependent manner with 3' to 5' polarity (14, 15).

Last updated: 2007-08-30 Contact SGD

References cited on this page View Complete Literature Guide for MCM4
1) Merchant AM, et al.  (1997) A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Mol Cell Biol 17(6):3261-71
2) Coxon A, et al.  (1992) Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication. Nucleic Acids Res 20(21):5571-7
3) Hennessy KM, et al.  (1991) A group of interacting yeast DNA replication genes. Genes Dev 5(6):958-69
4) Tye BK  (1999) MCM proteins in DNA replication. Annu Rev Biochem 68:649-86
5) Tanaka S and Diffley JF  (2002) Interdependent nuclear accumulation of budding yeast Cdt1 and Mcm2-7 during G1 phase. Nat Cell Biol 4(3):198-207
6) Ma X, et al.  (2010) The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function. BMC Biochem 11():37
7) Bochman ML and Schwacha A  (2008) The Mcm2-7 complex has in vitro helicase activity. Mol Cell 31(2):287-93
8) Kearsey SE and Labib K  (1998) MCM proteins: evolution, properties, and role in DNA replication. Biochim Biophys Acta 1398(2):113-36
9) Moir D, et al.  (1982) Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies. Genetics 100(4):547-63
10) Yan H, et al.  (1991) Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes Dev 5(6):944-57
11) Dalton S and Whitbread L  (1995) Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast. Proc Natl Acad Sci U S A 92(7):2514-8
12) Wilmes GM and Bell SP  (2002) The B2 element of the Saccharomyces cerevisiae ARS1 origin of replication requires specific sequences to facilitate pre-RC formation. Proc Natl Acad Sci U S A 99(1):101-6
13) Kawasaki Y, et al.  (2006) Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro. Genes Cells 11(7):745-56
14) Davey MJ, et al.  (2003) Reconstitution of the Mcm2-7p heterohexamer, subunit arrangement, and ATP site architecture. J Biol Chem 278(7):4491-9
15) Biswas-Fiss EE, et al.  (2005) The Mcm467 complex of Saccharomyces cerevisiae is preferentially activated by autonomously replicating DNA sequences. Biochemistry 44(8):2916-25
16) Aparicio OM, et al.  (1997) Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell 91(1):59-69
17) Hennessy KM, et al.  (1990) Subcellular localization of yeast CDC46 varies with the cell cycle. Genes Dev 4(12B):2252-63
18) Chen Y, et al.  (1992) CDC46/MCM5, a yeast protein whose subcellular localization is cell cycle-regulated, is involved in DNA replication at autonomously replicating sequences. Proc Natl Acad Sci U S A 89(21):10459-63
19) Nguyen VQ, et al.  (2000) Clb/Cdc28 kinases promote nuclear export of the replication initiator proteins Mcm2-7. Curr Biol 10(4):195-205