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Gene Review

Hus1  -  Hus1 homolog (S. pombe)

Mus musculus

Synonyms: Checkpoint protein HUS1, mHUS1
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Disease relevance of Hus1


High impact information on Hus1

  • Hus1p is phosphorylated in response to DNA damage, and this requires rad3+ and each of the other checkpoint rad genes [3].
  • In this study we examined how targeted deletion of Hus1 affects cell cycle checkpoint responses to genotoxic stress [4].
  • However, when treated with DNA strand break-inducing agents such as ionizing radiation (IR), Hus1-deficient cells showed intact S-phase checkpoint responses [4].
  • Whereas wild-type cells transiently repressed DNA replication in response to benzo(a)pyrene dihydrodiol epoxide (BPDE), a genotoxin that causes bulky DNA adducts, Hus1-null cells maintained relatively high levels of DNA synthesis following treatment with this agent [4].
  • Taken together, these results demonstrate that Hus1 is required specifically for one of two separable mammalian checkpoint pathways that respond to distinct forms of genome damage during S phase [4].

Biological context of Hus1


Anatomical context of Hus1

  • By the use of quantitative telomere-length measurements, we demonstrate severe telomeric shortening in both Hus1-deficient mouse embryonic fibroblasts and thymocytes from conditional Hus1-knockout mice [7].
  • Mouse Hus1 was mapped to the proximal end of chromosome 11 and is therefore a candidate gene for the mouse mutation germ cell deficient, which maps to the same genomic region [8].
  • However, viable conditional Hus1 knockout mice consistently showed the greatest degree of Hus1 inactivation specifically in lung and mammary gland, highlighting varying requirements for Hus1 in different tissues [1].

Regulatory relationships of Hus1


  1. Conditional inactivation of the mouse Hus1 cell cycle checkpoint gene. Levitt, P.S., Liu, H., Manning, C., Weiss, R.S. Genomics (2005) [Pubmed]
  2. Increased common fragile site expression, cell proliferation defects, and apoptosis following conditional inactivation of mouse Hus1 in primary cultured cells. Zhu, M., Weiss, R.S. Mol. Biol. Cell (2007) [Pubmed]
  3. Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is phosphorylated in response to DNA damage. Kostrub, C.F., Knudsen, K., Subramani, S., Enoch, T. EMBO J. (1998) [Pubmed]
  4. Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Weiss, R.S., Leder, P., Vaziri, C. Mol. Cell. Biol. (2003) [Pubmed]
  5. Hus1 acts upstream of chk1 in a mammalian DNA damage response pathway. Weiss, R.S., Matsuoka, S., Elledge, S.J., Leder, P. Curr. Biol. (2002) [Pubmed]
  6. Involvement of Hus1 in the chain elongation step of DNA replication after exposure to camptothecin or ionizing radiation. Wang, X., Guan, J., Hu, B., Weiss, R.S., Iliakis, G., Wang, Y. Nucleic Acids Res. (2004) [Pubmed]
  7. Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage-checkpoint complex. Francia, S., Weiss, R.S., Hande, M.P., Freire, R., d'Adda di Fagagna, F. Curr. Biol. (2006) [Pubmed]
  8. Mouse Hus1, a homolog of the Schizosaccharomyces pombe hus1+ cell cycle checkpoint gene. Weiss, R.S., Kostrub, C.F., Enoch, T., Leder, P. Genomics (1999) [Pubmed]
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