Phospho-RAD17 (Ser635)

The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]

Full Name

RAD17 Checkpoint Clamp Loader Component

Function

Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Has a weak ATPase activity required for binding to chromatin. Participates in the recruitment of the RAD1-RAD9-HUS1 complex and RHNO1 onto chromatin, and in CHEK1 activation. May also serve as a sensor of DNA replication progression, and may be involved in homologous recombination.

Biological Process

Cellular response to DNA damage stimulusManual Assertion Based On ExperimentIMP:UniProtKB
DNA damage checkpoint signalingManual Assertion Based On ExperimentIBA:GO_Central
DNA repairManual Assertion Based On ExperimentIBA:GO_Central
DNA replication checkpoint signalingManual Assertion Based On ExperimentTAS:ProtInc
Mitotic DNA replication checkpoint signalingManual Assertion Based On ExperimentIBA:GO_Central
Mitotic intra-S DNA damage checkpoint signalingManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Nucleus
Phosphorylated form redistributes to discrete nuclear foci upon DNA damage.

PTM

Phosphorylated. Phosphorylation on Ser-646 and Ser-656 is cell cycle-regulated, enhanced by genotoxic stress, and required for activation of checkpoint signaling. Phosphorylation is mediated by ATR upon UV or replication arrest, whereas it may be mediated both by ATR and ATM upon ionizing radiation. Phosphorylation on both sites is required for interaction with RAD1 but dispensable for interaction with RFC3 or RFC4.