RAD1 homolog

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

RAD1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRAD1, HREC1, RAD1 homolog, RAD1 checkpoint DNA exonuclease
External IDsOMIM: 603153 MGI: 1316678 HomoloGene: 37695 GeneCards: RAD1
EC number3.1.11.2
Orthologs
SpeciesHumanMouse
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 MbChr 15: 10.49 – 10.5 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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:

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. The Exonuclease Homolog OsRAD1 Promotes Accurate Meiotic Double-Strand Break Repair by Suppressing Nonhomologous End Joining. Plant Physiol. 2016 Oct;172(2):1105-1116. doi: 10.1104/pp.16.00831. Epub 2016 Aug 10. PMID: 27512017; PMCID: PMC5047095
  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. Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis. Elife. 2022 Feb 8;11:e68677. doi: 10.7554/eLife.68677. PMID: 35133274; PMCID: PMC8824475
  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

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