CDC45 DNA replication initiation factor CDC45 [Saccharomyces cerevisiae S288C] - Gene

Summary

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Gene symbol: CDC45
Gene description: DNA replication initiation factor CDC45
Primary source: SGD:S000004093
Locus tag: YLR103C
See related: AllianceGenome:SGD:S000004093
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Saccharomyces cerevisiae S288C (strain: S288C)
Lineage: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces
Also known as: SLD4
Summary: Enables DNA replication origin binding activity; chromatin binding activity; and single-stranded DNA binding activity. Involved in DNA replication initiation and double-strand break repair via break-induced replication. Located in nuclear replication fork. Part of CMG complex and replication fork protection complex. Used to study Meier-Gorlin syndrome. Human ortholog(s) of this gene implicated in Meier-Gorlin syndrome 7. Orthologous to human CDC45 (cell division cycle 45). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

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Location:: chromosome: XII

Exon count:: 1

Sequence:: Chromosome: XII; NC_001144.5 (343989..345941, complement)

Chromosome XII - NC_001144.5 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:: NC_001144.5

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Using a Fkh1-dependent origin relocalization assay, the authors determine that execution of Dbf4-dependent kinase function, including Cdc45 loading, results in dynamic relocalization of a replication origin from the nuclear periphery to the interior in G1 phase.
Title: Dynamic relocalization of replication origins by Fkh1 requires execution of DDK function and Cdc45 loading at origins.
functional importance of Cdc45 domains
Title: Initiation-specific alleles of the Cdc45 helicase-activating protein.
Rad53 binds to forkhead-associated (FHA) interaction motifs in an unstructured loop region of Cdc45, which is phosphorylated by Rad53 itself, and this interaction is necessary for the inhibition of origin firing through Sld3. Cdc45 also recruits Rad53 to stalled replication forks, which we demonstrate is important for the response to replication stress.
Title: Helicase Subunit Cdc45 Targets the Checkpoint Kinase Rad53 to Both Replication Initiation and Elongation Complexes after Fork Stalling.
Data show that Dbf4-dependent kinase (DDK)-phosphoryled MCM DNA helicase complex subunit MCM2 preferentially interacts with DNA replication initiation factor CDC45.
Title: Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase.
Upon extrusion of ssDNA from the central channel of Mcm2-7, Dpb11 dissociates from Mcm2-7, and Dpb11 binds to ssDNA, thereby allowing GINS to bind to Cdc45.Mcm2-7
Title: Dpb11 protein helps control assembly of the Cdc45·Mcm2-7·GINS replication fork helicase.
cdc45-ssDNA interaction is important for stalling the helicase during replication stress
Title: Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress.
The low-abundance replication proteins Sld3, Sld7, and Cdc45 form a complex and associate with the early-firing origins in G1 phase in a manner that depends on Dbf4-dependent kinase (DDK), which is essential for the initiation of DNA replication.
Title: Origin association of Sld3, Sld7, and Cdc45 proteins is a key step for determination of origin-firing timing.
GINS (Psf1, Psf2, Psf3, and Sld5) and Sld3 compete with one another for Mcm2-7 and Cdc45 binding
Title: GINS and Sld3 compete with one another for Mcm2-7 and Cdc45 binding.

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Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Orthologs from OrthoDB

Gene Ontology Provided by SGD

Function	Evidence Code	Pubs
enables DNA replication origin binding	IBA Inferred from Biological aspect of Ancestor more info
enables DNA replication origin binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables single-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables single-stranded DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication	IEA Inferred from Electronic Annotation more info
involved_in DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication initiation	IEA Inferred from Electronic Annotation more info
involved_in DNA replication initiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in DNA replication initiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via break-induced replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair via break-induced replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic DNA replication preinitiation complex assembly	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of CMG complex	IDA Inferred from Direct Assay more info	PubMed
part_of DNA replication preinitiation complex	IBA Inferred from Biological aspect of Ancestor more info
part_of DNA replication preinitiation complex	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear replication fork	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of replication fork protection complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA replication initiation factor CDC45

NP_013204.1

DNA replication initiation factor; recruited to MCM pre-RC complexes at replication origins; promotes release of MCM from Mcm10p, recruits elongation machinery; binds tightly to ssDNA, which disrupts interaction with the MCM helicase and stalls it during replication stress; mutants in human homolog may cause velocardiofacial and DiGeorge syndromes