This entry represents Rad17 from budding yeast (the homologue of human and S. pombe Rad1). Rad17 is a component of the checkpoint clamp complex (Ddc1/Mec3/Rad17) involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes [, , ]. In S. cerevisiae, the Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway and the activation of Rad53 in response to DNA damage at phase G1 []. The complex also physically regulates DNA polymerase zeta-dependent mutagenesis by controlling the access of polymerase zeta to damaged DNA []. Contrary to its human counterpart, the 9-1-1 complex, the checkpoint clamp complex shows no detectable exonuclease activity []. It's worth noting that the name, Rad17, has been used for a different protein in human and S. pombe. The homologue of the human and S. pombe Rad17 in budding yeast is Rad24.
This entry represents checkpoint protein Rad24 from budding yeasts and its homologue, Rad17 from other organisms. In Saccharomyces cerevisiae, Rad24 forms a complex with replication factor C (RFC) proteins, including Rfc2, Rfc3, Rfc4, and Rfc5. When DNA damage is detected, the Rad24-RFC complex loads Rad17-Mec3-Ddc1 complex onto chromatin and activates DNA damage checkpoint, which then leads to cell cycle arrest and DNA repair []. The Rad24-RFC complex is involved in both the mitotic and meiotic checkpoints []. Besides checkpoint activation, Rad24 is also involved in double-strand break ends processing, DNA repair and telomere maintenance [, , , ]. In human, the comparable DNA damage checkpoint components, Rad17 and the Rad1-Rad9-Hus1 (9-1-1) complex, play similar roles in DNA damage surveillance and checkpoint activation as their counter partners (Rad24, Rad17-Mec3-Ddc1) in budding yeast. Rad17 participates in the recruitment of the 9-1-1 complex onto chromatin. Besides checkpoint activation, Rad17 may also serve as a sensor of DNA replication progression, and may be involved in homologous recombination []. Overexpression of Rad17 has been associated with human breast and colon cancers [, ]. It's worth noting that the name, Rad17, has been used for different proteins in budding yeast and other organisms. In this entry, Rad17, is the homologue of the budding yeast Rad24 and has no homology with budding yeast Rad17
This entry consists of the checkpoint protein Rad24 from budding yeast and its homologue, Rad17, from other organisms. This entry does not include Rad17 from plants. In Saccharomyces cerevisiae, Rad24 forms a complex with replication factor C (RFC) proteins, including Rfc2, Rfc3, Rfc4, and Rfc5. When DNA damage is detected, the Rad24-RFC complex loads Rad17-Mec3-Ddc1 complex onto chromatin and activates DNA damage checkpoint, which then leads to cell cycle arrest and DNA repair []. The Rad24-RFC complex is involved in both the mitotic and meiotic checkpoints []. Besides checkpoint activation, Rad24 is also involved in double-strand break ends processing, DNA repair and telomere maintenance [, , , ]. In human, the comparable DNA damage checkpoint components, Rad17 and the Rad1-Rad9-Hus1 (9-1-1) complex, play similar roles in DNA damage surveillance and checkpoint activation as their counter partners (Rad24, Rad17-Mec3-Ddc1) in budding yeast. Rad17 participates in the recruitment of the 9-1-1 complex onto chromatin. Besides checkpoint activation, Rad17 may also serve as a sensor of DNA replication progression, and may be involved in homologous recombination []. Overexpression of Rad17 has been associated with human breast and colon cancers [, ]. It's worth noting that the name, Rad17, has been used for different proteins in budding yeast and other organisms. In this entry, Rad17, is the homologue of the budding yeast Rad24 and has no homology with budding yeast Rad17
The function of the ATR-ATRIP (ATR-interacting protein) protein kinase complex is crucial for the cellular response to replication stress and DNA damage. ATRIP is a regulatory partner of ATR. The binding of ATRIP to replication protein A-coated ssDNA at sites of DNA damage drives ATR activation and enables the ATR-ATRIP complex to stimulate phosphorylation of substrates, such as Rad17 or Chk1, and the initiation of checkpoint signalling []. ATRIP deacetylation by SIRT2 promotes ATR-ATRIP bindingto RPA-ssDNA [].
SNI1 was isolated in a screen for negative regulators of NPR1, a transcriptional coactivator of plant pathogen defence gene PR1 []. SNl1 has been shown to cooperate with the transcription repressor CBNAC, which binds to cis-elements on the PR1 promoter, to suppress PR1 expression []. SNI1 also regulates DNA damage sensor proteins RAD17 and ATR, suggesting that DNA damage responses is an intrinsic component of the plant immune responses. SNI1 is a subunit of the Structural Maintenance of Chromosome (SMC) 5/6 complex involved in DNA damage responses [].
Rec1 of Ustilago maydis is a homologue of S. pombe Rad1 and S. cerevisiae Rad17 proteins. It plays a key role in regulating the genetic systemof the fungus. Rec1 mutants are very sensitive to UV light - mutationleads to a complex phenotype with alterations in DNA repair, recombination,mutagenesis, meiosis and cell division. The predicted product of theREC1 gene is a polypeptide of 522 amino acid residues with molecular mass 57 kD. The protein shows 3'--5' exonuclease activity, but only in cellsover-expressing Rec1. While it is distinguishable from the majorbacterial nucleases, the protein has certain enzymatic features in commonwith epsilon, the proof-reading exonuclease subunit of Escherichia coli DNA polymeraseIII holoenzyme [].
This family consists of the repair proteins Rad1, Rec1 and Rad17.Rad1 is a component of the 9-1-1 cell-cycle checkpoint response complex (Rad9-Rad1-Hus1) that plays a major role in DNA repair [, ]. Rad1 isoform 1 possesses 3'->5' double stranded DNA exonuclease activity [].Rec1 of Ustilago maydis plays a key role in regulating the genetic system of this fungus. Rec1 mutants are very sensitive to UV light. Mutation leads to a complex phenotype with alterations in DNA repair, recombination, mutagenesis, meiosis and cell division []. Rec1 shows 3'--5' exonuclease activity, but only in cells over-expressing Rec1. Rad17 is a budding yeast checkpoint protein. It is a component of the checkpoint clamp complex (composed of Ddc1, Mec3 and Rad17) involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes [, , ]. The Ddc1-Mec3-Rad17 clamp complex shows no detectable exonuclease activity [].
This entry represents the budding yeast Ddc1, which is homologous to the fission yeast and human Rad9.DNA-damage checkpoint protein 1 (Ddc1) forms a checkpoint clamp complex with Mec3 and Rad17 [, ]. This complex plays a role in the surveillance system that permits DNA-repair pathways to restore the integrity of DNA in advance of DNA synthesis or separation of replicated chromosomes, thereby ensuring that new phases are not entered if DNA is damaged []. Ddc1 can activate Mec1 (the principal checkpoint protein kinase, human ATR homologue) in G1 phase. In G2 phase, Ddc1 can either activate Mec1 directly or recruit Dpb11 (ortholog of human TopBP1) and subsequently activate Mec1 []. Ddc1 does not have the DNA exonuclease function [].
Rad1 is a component of the 9-1-1 cell-cycle checkpoint response complex, which plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress [, ]. The 9-1-1 complex is recruited to DNA lesions upon damage by the Rad17 (Rad24 in budding yeast)-replication factor C (RFC) clamp loader complex. The 9-1-1 complex is necessary for the recruitment of C12orf32/RHINO to sites of double-stranded breaks (DSB) occurring during the S phase []. Rad1 isoform 1 possesses 3'->5' double stranded DNA exonuclease activity [].In Caenorhabditis elegans, the cell cycle checkpoint protein RAD1 homologue mrt-2 has a role in genome stability by promoting DNA double strand break-induced cell cycle arrest and apoptosis, and is required for maintaining telomere length and germline immortality [, , ].
