RAD1 homolog

RAD1 checkpoint DNA exonuclease
Rendering based on PDB 3A1J​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3A1J​, 3G65​, 3GGR​
Identifiers
Symbols	RAD1 ; HRAD1; REC1
External IDs	OMIM: 603153 MGI: 1316678 HomoloGene: 37695 GeneCards: RAD1 Gene
EC number	3.1.11.2
Gene ontology Molecular function • damaged DNA binding • protein binding • 3'-5' exonuclease activity • exodeoxyribonuclease III activity Cellular component • nucleus • nucleoplasm • chromosome • checkpoint clamp complex • intracellular membrane-bounded organelle Biological process • DNA damage checkpoint • DNA replication • DNA repair • cellular response to DNA damage stimulus • substantia nigra development • meiotic recombination checkpoint • cellular response to ionizing radiation • nucleic acid phosphodiester bond hydrolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5810	19355
Ensembl	ENSG00000113456	ENSMUSG00000022248
UniProt	O60671	Q9QWZ1
RefSeq (mRNA)	NM_001033673	NM_001289447
RefSeq (protein)	NP_002844	NP_001276376
Location (UCSC)	Chr 5: 34.91 – 34.92 Mb	Chr 15: 10.49 – 10.5 Mb
PubMed search

Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.^[1][2][3]

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.^[3]

Interactions

RAD1 homolog has been shown to interact with:

• HUS1,^[4][5]
• RAD17,^[6][7][8] and
• RAD9A,^{[4][9][10][11][12]}

References

1. 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.
2. 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.
3. "Entrez Gene: RAD1 RAD1 homolog (S. pombe)".
4. 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.
5. 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.
6. 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. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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. 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. PMID 11573955.
• 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.
• 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.