RAD1 homolog

RAD1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A1J, 3G65, 3GGR
Identifiers
Aliases	RAD1, HREC1, RAD1 homolog, RAD1 checkpoint DNA exonuclease
External IDs	OMIM: 603153; MGI: 1316678; HomoloGene: 37695; GeneCards: RAD1; OMA:RAD1 - orthologs
EC number	3.1.11.2
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p13.2 Start 34,905,260 bp[1] End 34,918,989 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 A1 Start 10,486,104 bp[2] End 10,499,149 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte nipple urethra visceral pleura renal medulla superior surface of tongue ventral tegmental area pylorus cardia Achilles tendon Top expressed in embryo epiblast spermatocyte ventricular zone morula endocardial cushion ectoderm otic vesicle otic placode medial ganglionic eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function damaged DNA binding exodeoxyribonuclease III activity protein binding 3'-5' exonuclease activity nuclease activity exonuclease activity hydrolase activity Cellular component intracellular membrane-bounded organelle chromosome nucleoplasm checkpoint clamp complex nucleus Biological process substantia nigra development DNA damage checkpoint signaling cellular response to DNA damage stimulus DNA replication meiotic recombination checkpoint signaling cellular response to ionizing radiation nucleic acid phosphodiester bond hydrolysis regulation of signal transduction by p53 class mediator DNA repair Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5810 19355 Ensembl ENSG00000113456 ENSMUSG00000022248 UniProt O60671 Q9QWZ1 RefSeq (mRNA) NM_001033673 NM_002853 NM_133282 NM_133377 NM_001289447 NM_001289448 NM_011232 RefSeq (protein) NP_002844 NP_001276376 NP_001276377 NP_035362 Location (UCSC) Chr 5: 34.91 – 34.92 Mb Chr 15: 10.49 – 10.5 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.[5][6][7]

Function

This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.[7]

Meiosis

During meiosis, double-strand breaks occur in DNA that initiate recombination. Recombination is a process that repairs the breaks and also promotes faithful chromosome segregation.[8] In yeast the 9-1-1 complex (including RAD1) facilitates meiotic recombination. An alternative, but inaccurate, mechanism for repairing double-strand breaks is non-homologous end joining. In the rice plant, the 9-1-1 complex promotes accurate meiotic recombination by suppressing the alternative process of non-homologous end joining.[8]

During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes.[9] Testis-specific disruption of RAD1 in mice results in defective double-strand break repair, depletion of germ cells and infertility.[9]

Interactions

RAD1 homolog has been shown to interact with:

• HUS1,[10][11]
• RAD17,[12][13][14] and
• RAD9A,[10][15][16][17][18]

References

1. GRCh38: Ensembl release 89: ENSG00000113456 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022248 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Freire R, Murguía JR, Tarsounas M, Lowndes NF, Moens PB, Jackson SP (September 1998). "Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis". Genes Dev. 12 (16): 2560–73. doi:10.1101/gad.12.16.2560. PMC 317084. PMID 9716408.
6. Bluyssen HA, van Os RI, Naus NC, Jaspers I, Hoeijmakers JH, de Klein A (January 1999). "A human and mouse homolog of the Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene". Genomics. 54 (2): 331–7. doi:10.1006/geno.1998.5582. PMID 9828137.
7. "Entrez Gene: RAD1 RAD1 homolog (S. pombe)".
8. Hu Q, Tang D, Wang H, Shen Y, Chen X, Ji J, Du G, Li Y, Cheng Z (October 2016). "The Exonuclease Homolog OsRAD1 Promotes Accurate Meiotic Double-Strand Break Repair by Suppressing Nonhomologous End Joining". Plant Physiol. 172 (2): 1105–16. doi:10.1104/pp.16.00831. PMC 5047095. PMID 27512017.
9. Pereira C, Arroyo-Martinez GA, Guo MZ, Downey MS, Kelly ER, Grive KJ, Mahadevaiah SK, Sims JR, Faca VM, Tsai C, Schiltz CJ, Wit N, Jacobs H, Clark NL, Freire R, Turner J, Lyndaker AM, Brieno-Enriquez MA, Cohen PE, Smolka MB, Weiss RS (February 2022). "Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis". eLife. 11: e68677. doi:10.7554/eLife.68677. PMC 8824475. PMID 35133274.
10. Volkmer E, Karnitz LM (January 1999). "Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex". J. Biol. Chem. 274 (2): 567–70. doi:10.1074/jbc.274.2.567. PMID 9872989. S2CID 28787137.
11. Hang H, Zhang Y, Dunbrack RL, Wang C, Lieberman HB (April 2002). "Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1". Genomics. 79 (4): 487–92. doi:10.1006/geno.2002.6737. PMID 11944979.
12. Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A (February 2003). "Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro". Proc. Natl. Acad. Sci. U.S.A. 100 (4): 1633–8. Bibcode:2003PNAS..100.1633B. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
13. Rauen M, Burtelow MA, Dufault VM, Karnitz LM (September 2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID 10884395. S2CID 34505615.
14. Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF (June 2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature. 411 (6840): 969–74. doi:10.1038/35082110. PMID 11418864. S2CID 4429058.
15. Dufault VM, Oestreich AJ, Vroman BT, Karnitz LM (Dec 2003). "Identification and characterization of RAD9B, a paralog of the RAD9 checkpoint gene". Genomics. 82 (6): 644–51. doi:10.1016/s0888-7543(03)00200-3. PMID 14611806.
16. Griffith JD, Lindsey-Boltz LA, Sancar A (May 2002). "Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopy". J. Biol. Chem. 277 (18): 15233–6. doi:10.1074/jbc.C200129200. PMID 11907025. S2CID 24820773.
17. Hirai I, Wang HG (July 2002). "A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex". J. Biol. Chem. 277 (28): 25722–7. doi:10.1074/jbc.M203079200. PMID 11994305. S2CID 35202138.
18. Lindsey-Boltz LA, Bermudez VP, Hurwitz J, Sancar A (September 2001). "Purification and characterization of human DNA damage checkpoint Rad complexes". Proc. Natl. Acad. Sci. U.S.A. 98 (20): 11236–41. Bibcode:2001PNAS...9811236L. doi:10.1073/pnas.201373498. PMC 58713. PMID 11572977.

Further reading

• Bardwell AJ, Bardwell L, Johnson DK, Friedberg EC (1993). "Yeast DNA recombination and repair proteins Rad1 and Rad10 constitute a complex in vivo mediated by localized hydrophobic domains". Mol. Microbiol. 8 (6): 1177–88. doi:10.1111/j.1365-2958.1993.tb01662.x. PMID 8361362. S2CID 45135386.
• Parker AE, Van de Weyer I, Laus MC, Oostveen I, Yon J, Verhasselt P, Luyten WH (1998). "A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease". J. Biol. Chem. 273 (29): 18332–9. doi:10.1074/jbc.273.29.18332. PMID 9660799. S2CID 24604811.
• Udell CM, Lee SK, Davey S (1998). "HRAD1 and MRAD1 encode mammalian homologues of the fission yeast rad1(+) cell cycle checkpoint control gene". Nucleic Acids Res. 26 (17): 3971–6. doi:10.1093/nar/26.17.3971. PMC 147814. PMID 9705507.
• Marathi UK, Dahlen M, Sunnerhagen P, Romero AV, Ramagli LS, Siciliano MJ, Li L, Legerski RJ (1999). "RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene". Genomics. 54 (2): 344–7. doi:10.1006/geno.1998.5589. PMID 9828139.
• Volkmer E, Karnitz LM (1999). "Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex". J. Biol. Chem. 274 (2): 567–70. doi:10.1074/jbc.274.2.567. PMID 9872989. S2CID 28787137.
• Dean FB, Lian L, O'Donnell M (1999). "cDNA cloning and gene mapping of human homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster". Genomics. 54 (3): 424–36. doi:10.1006/geno.1998.5587. PMID 9878245.
• St Onge RP, Udell CM, Casselman R, Davey S (1999). "The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1". Mol. Biol. Cell. 10 (6): 1985–95. doi:10.1091/mbc.10.6.1985. PMC 25401. PMID 10359610.
• Hang H, Lieberman HB (2000). "Physical interactions among human checkpoint control proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression". Genomics. 65 (1): 24–33. doi:10.1006/geno.2000.6142. PMID 10777662.
• Cai RL, Yan-Neale Y, Cueto MA, Xu H, Cohen D (2000). "HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins". J. Biol. Chem. 275 (36): 27909–16. doi:10.1074/jbc.M000168200. PMID 10846170.
• Burtelow MA, Kaufmann SH, Karnitz LM (2000). "Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage". J. Biol. Chem. 275 (34): 26343–8. doi:10.1074/jbc.M001244200. PMID 10852904. S2CID 24638557.
• Rauen M, Burtelow MA, Dufault VM, Karnitz LM (2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID 10884395. S2CID 34505615.
• Burtelow MA, Roos-Mattjus PM, Rauen M, Babendure JR, Karnitz LM (2001). "Reconstitution and molecular analysis of the hRad9-hHus1-hRad1 (9-1-1) DNA damage responsive checkpoint complex". J. Biol. Chem. 276 (28): 25903–9. doi:10.1074/jbc.M102946200. PMID 11340080. S2CID 25624886.
• Bao S, Tibbetts RS, Brumbaugh KM, Fang Y, Richardson DA, Ali A, Chen SM, Abraham RT, Wang XF (2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature. 411 (6840): 969–74. doi:10.1038/35082110. PMID 11418864. S2CID 4429058.
• Xiang SL, Kumano T, Iwasaki SI, Sun X, Yoshioka K, Yamamoto KC (2001). "The J domain of Tpr2 regulates its interaction with the proapoptotic and cell-cycle checkpoint protein, Rad9". Biochem. Biophys. Res. Commun. 287 (4): 932–40. doi:10.1006/bbrc.2001.5685. hdl:2297/1794. PMID 11573955. S2CID 20694221.
• Zou L, Cortez D, Elledge SJ (2002). "Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin". Genes Dev. 16 (2): 198–208. doi:10.1101/gad.950302. PMC 155323. PMID 11799063.
• Griffith JD, Lindsey-Boltz LA, Sancar A (2002). "Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopy". J. Biol. Chem. 277 (18): 15233–6. doi:10.1074/jbc.C200129200. PMID 11907025. S2CID 24820773.
• Hang H, Zhang Y, Dunbrack RL, Wang C, Lieberman HB (2002). "Identification and characterization of a paralog of human cell cycle checkpoint gene HUS1". Genomics. 79 (4): 487–92. doi:10.1006/geno.2002.6737. PMID 11944979.
• Hirai I, Wang HG (2002). "A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex". J. Biol. Chem. 277 (28): 25722–7. doi:10.1074/jbc.M203079200. PMID 11994305. S2CID 35202138.