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FLASH GENE

Symbol

RAD17

contributors: mct - updated : 30-10-2015

HGNC name	RAD17 homolog (S. pombe)
HGNC id	9807

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	5q13.2      Physical location : 68.665.123 - 68.710.626
Synonym name	RF-C activator 1 homolog
	cell cycle checkpoint protein (RAD17)
Synonym symbol(s)	RAD24, RAD17sp, CCYC, FLJ41520, R24L

DNA

TYPE	functioning gene
STRUCTURE	45.73 kb     18 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	four alternatively spliced isoforms (Chen 2001)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_133338 19 splicing 3076 NP_579916 75.7 670 - 2001 11602352 NM_002873 17 - 3164 NP_002864 75.7 670 - 2001 11602352 NM_133339 16 splicing 2633 NP_579917 77 681 - 2001 11602352 NM_133340 16 splicing 2666 NP_579918 57.1 505 - 2001 11602352 NM_133341 16 - 2592 NP_579919 66 584 - 2001 11602352 NM_133342 18 - 2972 NP_579920 75.7 670 - 2001 11602352 NM_133343 18 - 3010 NP_579921 75.7 670 - 2001 11602352 NM_133344 17 - 2842 NP_579922 75.7 670 - 2001 11602352

EXPRESSION

Type

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 Reproductive male system testis     highly

cell lineage
cell lines	cancer cell lines (in colon carcinoma)
fluid/secretion	seminoma

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	potential a N terminal P-loop binding consensus sequence
	a Walker B motif

HOMOLOGY

interspecies	homolog to yeast S.pombe RAD17
	homolog to yeast S.cerevisiae RAD24
	homolog to murine Rad24
	homolog to murine Rad17

Homologene

FAMILY

rad17/RAD24 family

CATEGORY

regulatory , DNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	cell cycle G2 checkpoint control gene, required for S-phase and G2/M arrest in response to DNA damage or incomplete DNA replication
	centrally involved in the activation of cell-cycle checkpoints by genotoxic agents or replication stress
	phosphorylation-dependent function of RAD17 in an ATR-RAD17-Claspin-CHEK1-signaling cascade that responds to specific replication stress
	similarly to other human genes involved in checkpoint mechanisms, plays a role in control of tumor growth
	critical for the ATR-dependent activation of CHEK1 during checkpoint responses
	exhibiting a distinctive pattern of upregulation followed by subsequent degradation after exposure to UV radiation in primary cells
	its stabilization prevents the termination of checkpoint signalling, which in turn attenuates the cellular re-entry into cell-cycle progression

CELLULAR PROCESS	cell cycle, checkpoint
	nucleotide, repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

RAD17/RAD3/RAD1, is the 9-1-1 complex

INTERACTION

DNA

RNA

small molecule

protein	interacting with RAD1 (interaction protein-protein in the cell cycle checkpoint machinery)
	MCM7, a core component of the DNA replication apparatus, is a novel RAD17-interacting protein
	phosphorylated RAD17 interacts with Claspin and regulates its phosphorylation
	plays a central role in establishment of the interaction between TOPBP1 and the RAD9A-HUS1-RAD1 complex at stalled replication forks
	Claspin and RAD17 are reportedly involved in the DNA damage-induced phosphorylation of CHEK1, a hallmark of checkpoint activation
	RAD9A is loaded by RAD17 onto damaged chromatin
	USP20 is required for RAD17 protein stability in the steady-state and post DNA damage
	gain of function mutant TP53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression

cell & other

REGULATION

Other

phosphorylation by ATR is important for genomic stability and restraint of S phase but is not essential for cell survival

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         in head and neck cancer, is often due to genomic deletion, and may facilitate genomic instability in head and neck cancer

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS