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FLASH GENE

Symbol

CDT1

contributors: mct - updated : 23-03-2013

HGNC name	chromatin licensing and DNA replication factor 1
HGNC id	24576

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	5.48 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_030928 10 - 2742 NP_112190 60.4 546 - 2008 18162579

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver       highly Lymphoid/Immune thymus       highly Reproductive female system uterus cervix   predominantly

cell lineage

cell lines

fluid/secretion

at STAGE

cell cycle

cell cycle, G1, S

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a PCNA-binding motif called a PIP box

conjugated

Other

HOMOLOGY

interspecies	homolog to murine Cdt1 (76.3pc)
	homolog to rattus Cdt1 (74.5pc)

Homologene

FAMILY

Cdt1 family

CATEGORY

regulatory , DNA associated , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome
text	replication fork

basic FUNCTION	cooperating with CDC6 to promote the loading of the mini-chromosome maintenance complex onto chromatin to form the pre-replication complex necessary to initiate DNA replication
	potential oncogene, overexpression of CDT1 promotes rereplication and generates a DNA damage response which activates the anti tumors barriers of senescence and apoptosis
	major platform on the pre-replication complexes to integrate cell cycle signals
	with CDC6 are destabilized by rereplication-induced DNA damage
	is required for the formation of the pre-replicative complexes ssociating with the CDC7 kinase and recruiting CDC45 to chromatin during S phase (chromatin-bound CDT1 is first stabilized and subsequently displaced by CDC7 activity)
	present during the G1 phase of the cell cycle

CELLULAR PROCESS	cell cycle, checkpoint
	nucleotide, replication

PHYSIOLOGICAL PROCESS

text	DNA replication checkpoint
	regulation of DNA replication initiation

PATHWAY

metabolism

signaling

a component	part of pre-replication complex
	CDT1-GMNN complex likely acts as a molecular switch that can enable or disable the firing of each origin of replication

INTERACTION

DNA	binding DNA in a sequence-, strand-, and conformation-independent manner

RNA

small molecule

protein	GMNN
	DDB1
	interaction of CDT1 with ORCs is involved in the formation of the prereplicative complex, rather than in regulation of the activity of ORCs
	DTL is a conserved component of the Cul4-DDB1 E3 that is essential to destroy CDT1 and ensure proper cell cycle regulation and timing of DNA replication
	forming a stable complex with MCM9
	PCNA promotes the DNA damage-induced degradation of the replication initiation factor CDT1 via the DTL E3 ubiquitin ligase complex
	directly interacting with MYST2, coactivator of CDT1
	DTL is a substrates of CDT1
	KAT7 is a coactivator both for AP-1 transcription factors responding to stress-activated JNK kinases and also for the CDT1 licensing factor that ensures that DNA is replicated exactly once per cell cycle
	unique role of FOXO3 in binding to CDT1 and maintaining its level required for cell cycle progression
	CDT1 cooperates with the cell cycle protein CDC6 to promote loading of the minichromosome maintenance helicases (MCM) onto the chromatin-bound origin recognition complex (ORC)
	ATR, activated after DNA damage, phosphorylates DTL and promotes the rapid degradation of CDT1 after UV irradiation in the G1 phase of the cell cycle
	CDT1 overexpression targets GMNN to the nucleus, while reducing CDT1 levels by RNAi leads to the appearance of endogenous GMNN in the cytoplasm
	GMNN is thought to be involved in licensing replication by promoting the accumulation of CDT1 in mitosis, because decreasing the GMNN levels prevents CDT1 accumulation and impairs DNA replication

cell & other

REGULATION

Other	PCNA is a cofactor for CDT1 degradation
	CDT2 interacts with CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis
	DDB1 is involved in the regulation of CDT1 degradation
	nucleotide excision repair factors promote CDT1 destruction due to a role in recruiting PCNA to damaged DNA (

ASSOCIATED DISORDERS

corresponding disease(s)

MGORS4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         CDT1 (and GMNN) expression is deregulated in tumor specimens and may represent novel markers useful for cancer diagnosis and prognosis

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS