cell cycle checkpoint protein RAD17 (hRad17, RF-C/activator 1 homolog, RAD17, R24L)
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Function
- sustained cell growth
- maintenance of chromosomal stability
- ATR-dependent checkpoint activation upon DNA damage
- weak ATPase activity required for binding to chromatin
- recruitment of the RAD1-RAD9-HUS1 complex onto chromatin
- CHEK1 activation
- sensor of DNA replication progression (putative)
- homologous recombination (putative)
- component of a DNA-binding complex containing RFC2, RFC3, RFC4, RFC5
- interacts with RAD1 & RAD9 within the RAD1-RAD9-HUS1 complex
- interacts with RAD9B, POLE, NHP2L1, MCM7
- DNA damage promotes interaction with ATR or ATM & disrupts interaction with the RAD1-RAD9-HUS1 complex
- induced by X-ray irradiation (isoform 1, 3 & 4)
- phosphorylation on Ser-646 & Ser-656 is cell cycle-regulated, enhanced by genotoxic stress, & required for activation of checkpoint signaling
- phosphorylation is mediated by ATR upon UV or replication arrest; it may be mediated both by ATR & ATM upon ionizing radiation
- phosphorylation on Ser-646 & Ser-656 is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4
Compartment
- nucleus
- phosphorylated form redistributes to discrete nuclear foci upon DNA damage
Alternative splicing
named isoforms=4 isoforms 2 & 3 are most abundant isoforms in non irradiated cells
Expression
- ubiquitous at low levels
- highly expressed in testis, within germinal epithelium of the seminiferous tubules
Pathology
- overexpressed in various cancer cell lines
- overexpressed incolon carcinoma (at protein level)
- weakly expressed in seminomas