Cdt1 chromatin licensing and DNA replication factor 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cdt1provided by MGI
Official Full Name: chromatin licensing and DNA replication factor 1provided by MGI
Primary source: MGI:MGI:1914427
See related: Ensembl:ENSMUSG00000006585 AllianceGenome:MGI:1914427
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: DUP; Ris2; 2610318F11Rik
Summary: Enables DNA binding activity. Involved in DNA replication checkpoint signaling and regulation of DNA-dependent DNA replication initiation. Acts upstream of or within regulation of nuclear cell cycle DNA replication. Located in nucleus. Is expressed in adrenal medulla; brain ventricular layer; dorsal root ganglion; liver; and trunk mesenchyme derived from neural crest. Human ortholog(s) of this gene implicated in Meier-Gorlin syndrome 4. Orthologous to human CDT1 (chromatin licensing and DNA replication factor 1). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in thymus adult (RPKM 48.2), liver E14.5 (RPKM 44.9) and 21 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 E1; 8 71.91 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (123294754..123299869)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (122568015..122573130)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CDT1 drives replication overlicensing and enhances tumorigenesis in the gut[dagger].
Title: CDT1 drives replication overlicensing and enhances tumorigenesis in the gut(†).
Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage.
Title: Cdt1 overexpression drives colorectal carcinogenesis through origin overlicensing and DNA damage.
conserved arginine residues play critical roles in interaction with Geminin and Mcm that are crucial for proper conformation of the complexes and its licensing activity.
Title: Characterization of conserved arginine residues on Cdt1 that affect licensing activity and interaction with Geminin or Mcm complex.
Study shows that ablation of Geminin induces massive rereplication as a result of unrestrained Cdt1 activity in embryonic stem cells, whereas it has no such effect in embryonic fibroblasts in which alternative regulation of Cdt1 activity is intact.
Title: Geminin is an indispensable inhibitor of Cdt1 in mouse embryonic stem cells.
This study reveals a conserved new regulatory Cdt1 domain crucial for proper DNA licensing activity.
Title: A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing.
Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable the identification of key residues for binding to replicative helicase Mcm proteins.
Title: Structure and mutagenesis studies of the C-terminal region of licensing factor Cdt1 enable the identification of key residues for binding to replicative helicase Mcm proteins.
Determined the structures of mCdt1CS (mCdt1C_small; residues 452 to 557) and mCdt1CL (mCdt1C_large; residues 420 to 557) using X-ray crystallography and NMR. This study reveals that Cdt1 is formed with a tandem repeat of the winged helix domain.
Title: Structure of the Cdt1 C-terminal domain: conservation of the winged helix fold in replication licensing factors.
DNA binding and helicase activities of Mcm4/6/7 are significantly stimulated by Cdt1
Title: Cdt1 forms a complex with the minichromosome maintenance protein (MCM) and activates its helicase activity.
Hepatitis B virus X protein increases the Cdt1-to-geminin ratio inducing DNA re-replication and polyploidy
Title: Hepatitis B virus X protein increases the Cdt1-to-geminin ratio inducing DNA re-replication and polyploidy.
PcG complex 1, involving Rae28 and Cdt1, supports the activity of hematopoietic stem cells by enhancing cycling capability and hematopoietic activity through direct regulation of Geminin
Title: Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Spontaneous (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW545653 (e-PCR)
- UniSTS:179840

RH126034 (e-PCR)
- UniSTS:162746

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA polymerase binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA replication	IEA Inferred from Electronic Annotation more info
involved_in DNA replication checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication checkpoint signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication checkpoint signaling	ISO Inferred from Sequence Orthology more info
involved_in DNA replication preinitiation complex assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication preinitiation complex assembly	ISO Inferred from Sequence Orthology more info
involved_in attachment of mitotic spindle microtubules to kinetochore	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell cycle	IEA Inferred from Electronic Annotation more info
involved_in mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of DNA-templated DNA replication	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell cycle	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA replication	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated DNA replication	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chromatin binding	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated DNA replication initiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated DNA replication initiation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated DNA replication initiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of nuclear cell cycle DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in response to sorbitol	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in chromosome, centromeric region	IEA Inferred from Electronic Annotation more info
located_in kinetochore	ISO Inferred from Sequence Orthology more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info	PubMed

General protein information

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Preferred Names: DNA replication factor Cdt1

Names: double parked homolog; retroviral insertion site 2 protein; retroviral integration site 1; retroviral integration site 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_026014.3 → NP_080290.3 DNA replication factor Cdt1

See identical proteins and their annotated locations for NP_080290.3

Status: VALIDATED

Source sequence(s)

BC048076

Consensus CDS

CCDS22741.1

UniProtKB/Swiss-Prot

Q8BUQ1, Q8BX29, Q8R3V0, Q8R4E8, Q8R4E9

Related

ENSMUSP00000006760.3, ENSMUST00000006760.3

Conserved Domains (2) summary

cd08674
Location:181 → 364

Cdt1_m; The middle winged helix fold of replication licensing factor Cdt1 binds geminin to inhibit binding of the MCM complex to origins of replication and DNA

cd08767
Location:427 → 549

Cdt1_c; The C-terminal fold of replication licensing factor Cdt1 is essential for Cdt1 activity and directly interacts with MCM2-7 helicase