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 [, , ].
This entry includes XPF from animals, Rad1 from budding yeasts and Rad16 from fission yeasts. Human XPF is a catalytic component of a structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. It is involved in homologous recombination that assists in removing interstrand cross-link []. Budding yeast Rad1 and Rad10 form an endonuclease that specifically degrades single-stranded DNA [].
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 family includes Rad10 from budding yeasts, Swi10 from fission yeasts and ERCC-1 from animals andplants. All proteins in this family for which functions are known are components in a multiprotein endonuclease complex (usually made up of Rad1 and Rad10 homologues). This complex is used primarily for nucleotide excision repair but also for some aspects of recombination repair. In budding yeast, Rad10 works as a heterodimer with Rad1, and is involved in nucleotide excision repair of DNA damaged with UV light, bulky adducts or cross-linking agents. The complex forms an endonuclease which specifically degrades single-stranded DNA [].ERCC1 and XPF (xeroderma pigmentosum group F-complementing protein) are two structure-specific endonucleases of a class of seven containing an ERCC4 domain. Together they form an obligate complex that functions primarily in nucleotide excision repair (NER), a versatile pathway able to detect and remove a variety of DNA lesions induced by UV light and environmental carcinogens, and secondarily in DNA inter-strand cross-link repair and telomere maintenance. This domain in fact binds simultaneously to both XPF and single-stranded DNA; this ternary complex explains the important role of Ercc1 in targeting its catalytic XPF partner to the NER pre-incision complex [].
This entry represents the DNA damage checkpoint protein Rad9 and its homologue in budding yeast, Ddc1. Rad9 forms a complex with Hus1 and Rad1 (called 9-1-1 complex). Ddc1 forms a similar complex with Mec1 and Rad17. Structurally, the 9-1-1 / Ddc1-Mec3-Rad17 complex is similar to the PCNA complex, which forms trimeric ring-shaped clamps. The 9-1-1 / Ddc1-Mec3-Rad17 complex plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress [, ].In humans, 9-1-1 binds to TopBP1 and activates the ATR-Chk1 checkpoint pathway []. Besides its function in the 9-1-1 complex, Rad9 can also act as a transcriptional factor and participate in immunoglobulin class switch recombination []. It also shows 3'-5' exonuclease activity []. Aberrant Rad9 expression has been associated with prostate, breast, lung, skin, thyroid, and gastric cancers [].In budding yeast, 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 (the orthologue of human TopBP1) and subsequently activate Mec1 []. Ddc1 does not have DNA exonuclease function [].It is worth noting that the Rad9 proteins referred to in this entry are the mammalian and fission yeast homologues of budding yeast Ddc1. Members of this family do not share the sequence homology another DNA damage-dependent checkpoint protein from budding yeast, confusingly also called Rad9.
