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Gene Review

RAD1  -  RAD1 checkpoint DNA exonuclease

Homo sapiens

Synonyms: Cell cycle checkpoint protein RAD1, DNA repair exonuclease rad1 homolog, HRAD1, REC1, Rad1-like DNA damage checkpoint protein, ...
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Disease relevance of RAD1


High impact information on RAD1

  • Plasmids containing Z-DNA stretches can be paired and linked by combined action of Ustilago rec1 protein and topoisomerase [5].
  • Equilibrium and kinetic studies show that rec1 protein appears to have a strong Z-DNA binding site that binds Z-DNA 75 times tighter than the B form of the DNA [6].
  • Synapsis promoted by Ustilago rec1 protein [7].
  • ATP-dependent reannealing of complementary single strands was not detectable in the rec1 mutant of Ustilago, which is deranged in meiotic recombination, as complete tetrads are rare, and is defective in radiation-induced mitotic gene conversion [8].
  • The human gene HRAD1 is located on chromosome 5p13 and is most homologous to S. pombe rad1(+) [9].

Biological context of RAD1


Anatomical context of RAD1

  • Northern blot analysis indicates that HUS1 is expressed in different tissues, but the mRNA is most predominant in testis where high levels of RAD1 and RAD9 message have been detected [13].
  • Mitoxantrone, a topoisomerase II inhibitor, induced a strong cytotoxic effect in three cell lines (JVM-2, REC-1, and Granta 519), and in primary MCL cells [14].
  • We sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes [15].
  • Our results suggest that culture-expanded hREC have the potential to colonize collagen-coated biomaterials and to regenerate epithelial cell types for tracheal tissue engineering [16].

Physical interactions of RAD1

  • The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1 [17].
  • Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells [18].

Regulatory relationships of RAD1


Other interactions of RAD1


Analytical, diagnostic and therapeutic context of RAD1


  1. RAD1, a human structural homolog of the Schizosaccharomyces pombe RAD1 cell cycle checkpoint gene. Marathi, U.K., Dahlen, M., Sunnerhagen, P., Romero, A.V., Ramagli, L.S., Siciliano, M.J., Li, L., Legerski, R.J. Genomics (1998) [Pubmed]
  2. A human and mouse homolog of the Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene. Bluyssen, H.A., van Os, R.I., Naus, N.C., Jaspers, I., Hoeijmakers, J.H., de Klein, A. Genomics (1998) [Pubmed]
  3. Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Bao, S., Lu, T., Wang, X., Zheng, H., Wang, L.E., Wei, Q., Hittelman, W.N., Li, L. Oncogene (2004) [Pubmed]
  4. Potassium antimonyl tartrate induces caspase- and reactive oxygen species-dependent apoptosis in lymphoid tumoral cells. Lecureur, V., Le Thiec, A., Le Meur, A., Amiot, L., Drenou, B., Bernard, M., Lamy, T., Fauchet, R., Fardel, O. Br. J. Haematol. (2002) [Pubmed]
  5. Homologous pairing of DNA molecules by Ustilago rec1 protein is promoted by sequences of Z-DNA. Kmiec, E.B., Holloman, W.K. Cell (1986) [Pubmed]
  6. Left-handed DNA and the synaptic pairing reaction promoted by Ustilago rec1 protein. Kmiec, E.B., Angelides, K.J., Holloman, W.K. Cell (1985) [Pubmed]
  7. Synapsis promoted by Ustilago rec1 protein. Kmiec, E.B., Holloman, W.K. Cell (1984) [Pubmed]
  8. Homologous pairing of DNA molecules promoted by a protein from Ustilago. Kmiec, E., Holloman, W.K. Cell (1982) [Pubmed]
  9. Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis. Freire, R., Murguía, J.R., Tarsounas, M., Lowndes, N.F., Moens, P.B., Jackson, S.P. Genes Dev. (1998) [Pubmed]
  10. The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9. Rauen, M., Burtelow, M.A., Dufault, V.M., Karnitz, L.M. J. Biol. Chem. (2000) [Pubmed]
  11. The two DNA clamps Rad9/Rad1/Hus1 complex and proliferating cell nuclear antigen differentially regulate flap endonuclease 1 activity. Friedrich-Heineken, E., Toueille, M., Tännler, B., Bürki, C., Ferrari, E., Hottiger, M.O., Hübscher, U. J. Mol. Biol. (2005) [Pubmed]
  12. Analysis of trinucleotide-repeat combination polymorphism at the rad gene in patients with type 2 diabetes mellitus. Yuan, X., Yamada, K., Ishiyama-Shigemoto, S., Koyama, W., Nonaka, K. Metab. Clin. Exp. (1999) [Pubmed]
  13. Physical interactions among human checkpoint control proteins HUS1p, RAD1p, and RAD9p, and implications for the regulation of cell cycle progression. Hang, H., Lieberman, H.B. Genomics (2000) [Pubmed]
  14. Activation of mitochondrial apoptotic pathway in mantle cell lymphoma: high sensitivity to mitoxantrone in cases with functional DNA-damage response genes. Ferrer, A., Marcé, S., Bellosillo, B., Villamor, N., Bosch, F., López-Guillermo, A., Espinet, B., Solé, F., Montserrat, E., Campo, E., Colomer, D. Oncogene (2004) [Pubmed]
  15. Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro. Rymaszewski, Z., Cohen, R.M., Chomczynski, P. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  16. Changes in the gene expression pattern of cytokeratins in human respiratory epithelial cells during culture. Endres, M., Leinhase, I., Kaps, C., Wentges, M., Unger, M., Olze, H., Ringe, J., Sittinger, M., Rotter, N. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2005) [Pubmed]
  17. The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1. St Onge, R.P., Udell, C.M., Casselman, R., Davey, S. Mol. Biol. Cell (1999) [Pubmed]
  18. Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells. Wu, X., Shell, S.M., Zou, Y. Oncogene (2005) [Pubmed]
  19. The human Rad9-Rad1-Hus1 checkpoint complex stimulates flap endonuclease 1. Wang, W., Brandt, P., Rossi, M.L., Lindsey-Boltz, L., Podust, V., Fanning, E., Sancar, A., Bambara, R.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event. Roos-Mattjus, P., Vroman, B.T., Burtelow, M.A., Rauen, M., Eapen, A.K., Karnitz, L.M. J. Biol. Chem. (2002) [Pubmed]
  21. A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease. Parker, A.E., Van de Weyer, I., Laus, M.C., Oostveen, I., Yon, J., Verhasselt, P., Luyten, W.H. J. Biol. Chem. (1998) [Pubmed]
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