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FLASH GENE
Symbol CDC45 contributors: mct/npt - updated : 24-08-2016
HGNC name cell division cycle 45 homolog (S. cerevisiae)
HGNC id 1739
Corresponding disease
MGORS7 Meier-Gorlin syndrome 7
Location 22q11.21      Physical location : 19.467.413 - 19.508.134
Synonym name
  • CDC45-related protein
  • CDC45 (cell division cycle 45, S.cerevisiae, homolog)-like
  • cell division cycle 45-like 2
  • Synonym symbol(s) CDC45L2, PORC-PI-1, CDC45L
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head, opposite orientation
    text head to head with UFD1L
    STRUCTURE 41.33 kb     19 Exon(s)
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure
  • multiple ploydenylation sites
  • bidirectional transcriptional control region between UFD1L and CDC45L
  • MAPPING cloned Y linked N status confirmed
    Map cen - DGCR6 - SLC25A1 - DGCR2 - TSSK2 - DGCR14 - GSC2 - HIRA - UFD1L - CDC45 - CLDN5 - qter
    Authors McKie (98)
    regionally located in the Di George critical region
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2094 - 598 - 2014 24293646
    19 - 1938 - 566 - 2014 24293646
    15 - 1850 - 520 - 2014 24293646
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Digestiveliver   highly
    Reproductivemale systemtestis  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text liver highly
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to yeast S.cerevisiae CDC45P
    homolog to murine Cdc45l
    homolog to C.elegans c45g7.4
    Homologene
    FAMILY
  • CDC45 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    text
  • considerable portion of CDC45 localizes in a region other than the DNA replication forks in nuclei or it localizes on the replication forks but it is not fractionated with the fork proteins owing to its tight association with presumably nuclear scaffolds
  • basic FUNCTION
  • playing a pivotal role in the loading of DNA polymerase alpha onto chromatin
  • required for initiation of chromosomal DNA replication
  • essential protein required to trigger initiation of DNA replication in late G1 phase (Kukimoto 1999)
  • acts as a molecular tether to mediate loading of the DNA polymerase alpha on to the DNA replication complex through binding to MCM7 (Kukimoto 1999)
  • has a central role in the regulation of the initiation and elongation stages of eukaryotic chromosomal DNA replication (Broderick 2009)
  • is an essential protein conserved in all eukaryotes and is involved both in the initiation of DNA replication and the progression of the replication fork
  • essential replication factor that, together with the MCM2-7 complex and the four subunits of GINS, forms the replicative DNA helicase in eukaryotes
  • not only binds to but also slides on DNA with a 3pime-5prime polarity and, thereby acts as a molecular 'wedge' to initiate DNA strand displacement
  • is limiting for replication initiation
  • is required for DNA synthesis during genome duplication, as a component of the CDC45-MCM-GINS (CMG) helicase
  • CELLULAR PROCESS cell cycle
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CDC45, MCM and CDC6 form a complex for initiation of DNA replication
  • CDC45/MCM2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase
  • component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself
  • INTERACTION
    DNA like the RECJ exonucleases, CDC45 protein is able to bind single-stranded, but not double-stranded DNA
    RNA
    small molecule
    protein
  • bind directly to minichromosome maintenance 7 protein (MCM7) and to the p70 subunit of DNA polymerase alpha (Kukimoto 1999)
  • DNA polymerase alpha
  • ORC2L
  • associates with CDT1 and CDC7 kinase (CDT1 recruiting CDC45 to chromatin) (Ballabeni 2009)
  • interacting with TOPBP1 (required for chromatin loading of the replication protein CDC45) (Schmidt 2008)
  • interacts with the putative eukaryotic replicative DNA helicase, the MCM (mini-chromosome maintenance) complex, and forms a helicase active 'supercomplex', the CMG [Cdc45-MCM2-7-GINS (go-ichi-ni-san)] complex (Broderick 2009)
  • coordinated binding of DTD1 and CDC45 to origins and the physical interactions of DTD1, CDC45, and TOPBP1 suggest that complexes of these proteins are necessary for replication initiation
  • GINS1, GINS2, GINS3, GINS4 and TICRR compete with one another for MCM2-7 and CDC45 binding
  • is a critical effector of myc-dependent DNA replication stress
  • MCM10 and CDC45 directly interact and establish a mutual co-operation in DNA binding
  • HELB interacts directly with two initiation factors TOPBP1 and CDC45 (both, the N-terminus and helicase domain of HELB bind to the N-terminus of CDC45)
  • initiation factor TICRR coordinating the assembly and activation of the eukaryotic replication fork helicase by recruiting CDC45 to MCM2-7
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MGORS7
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS