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FLASH GENE

Symbol

CHTF18

contributors: mct/npt - updated : 10-04-2018

HGNC name	CTF18, chromosome transmission fidelity factor 18 homolog (S. cerevisiae)
HGNC id	18435

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 Endocrine thyroid         Reproductive female system ovary     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone     highly

cell lineage
cell lines	hepatocellular carcinoma, medulloblastoma
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal nuclear localization signal (NLS)
	a proline rich domain
	a NTPase domain
	a RFC domain
	an ankyrin repeat domain
	two leucine zipper motifs
	C-terminal 23-AA stretch of CHTF18 was necessary for the trimeric association of complex CHTF18, DCC1, and CHTF8 and was required for the stable interaction

mono polymer

complex

HOMOLOGY

interspecies

homolog to yeast Chl12

Homologene

FAMILY	activator 1 small subunits family
	CTF18 subfamily

CATEGORY

DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome,heterochromosome
text	with ATAD5, localize to chromatin and ATAD5 plays a role in the recruitment of CHTF18 (Parnas 2009)

basic FUNCTION	having ATP binding activity
	may be involved in cohesion establishment during S phase
	binds chromatin during S phase suggesting a role during replication
	involved in damage-induced homologous recombination
	with WDHD1, and ATAD5 may coordinate the relative movement of the replication fork with respect to the cohesin ring (Parnas 2009)
	CHTF18 confers likely protection against stalling and/or breaks at the replication fork in cells that either lack, or are compromised for, telomerase activity
	CHTF18-RFC1 clamp loader contains a unique module in which the DSCC1-CHTF8 complex is bound to the C terminus of CHTF18 (the CHTF18-DSCC1-CHTF8 module)

CELLULAR PROCESS

nucleotide, replication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	alternative CHTF18-DSCC1-CHTF8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA (Bermudez 2003)
	C-terminal 23-AA stretch of CHTF18 was necessary for the trimeric association of complex CHTF18, DSCC1, and CHTF8 and was required for the stable interaction

INTERACTION

DNA	DNA binding

RNA

small molecule
	ATP

protein	PCNA
	forming a complex with CTF8 and DSCC1
	CHTF18-RFC1, stimulates DNA polymerase eta activity
	CHTF18-RFC1 has multiple interactions with POLE that promote polymorphic modulation of DNA synthesis
	association of CHTF18-RFC1 with POLE at defective replication forks is a key step in activation of the S-phase checkpoint
	interacts with replication protein A (RPA1) in response to replication stress
	CHTF18-RFC1 appears to be involved in leading-strand DNA synthesis through its interaction with POLE, and can load PCNA onto DNA when POLE is not in DNA synthesis mode to restore DNA synthesis
	CHTF18-RFC1 is an alternative PCNA loader which plays important but poorly understood roles in multiple DNA replication-associated processes

cell & other

REGULATION

Other

increases as cells progress through S phase

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       could lead to the chromosomal instability known as a hallmark of most cancers

Susceptibility

Variant & Polymorphism

Candidate gene	for cancer predisposition because of loss leading to abnormal yet viable phenotype
Marker
Therapy target

ANIMAL & CELL MODELS