HUS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHUS1, hHUS1 checkpoint clamp component
External IDsOMIM: 603760 MGI: 1277962 HomoloGene: 37932 GeneCards: HUS1
Orthologs
SpeciesHumanMouse
Entrez

3364

15574

Ensembl

ENSG00000136273

ENSMUSG00000020413

UniProt

O60921

Q8BQY8

RefSeq (mRNA)

NM_004507
NM_001363683

NM_008316
NM_001303532
NM_001303610

RefSeq (protein)

NP_004498
NP_001350612

NP_001290461
NP_001290539
NP_032342

Location (UCSC)Chr 7: 47.96 – 47.98 MbChr 11: 8.94 – 8.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene.[5][6]

Function

The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event.[7]

In somatic cells

In somatic cells the RAD9-RAD1-HUS1 (9-1-1) complex responds to DNA damage by promoting DNA repair.[8]

In meiosis

In flies, worms and yeast, the 9-1-1 complex is necessary for meiotic checkpoint function and efficient meiotic recombination.[8] During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes, double-strand break repair and cell cycle checkpoint signalling.[8][9]

Interactions

HUS1 has been shown to interact with:

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000136273 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020413 - 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. ↑ Dean FB, Lian L, O'Donnell M (Dec 1998). "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.
  6. ↑ Kostrub CF, Knudsen K, Subramani S, Enoch T (Apr 1998). "Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is phosphorylated in response to DNA damage". The EMBO Journal. 17 (7): 2055–66. doi:10.1093/emboj/17.7.2055. PMC 1170550. PMID 9524127.
  7. ↑ "Entrez Gene: HUS1 HUS1 checkpoint homolog (S. pombe)".
  8. 1 2 3 Lyndaker AM, Lim PX, Mleczko JM, Diggins CE, Holloway JK, Holmes RJ, et al. (2013). "Conditional inactivation of the DNA damage response gene Hus1 in mouse testis reveals separable roles for components of the RAD9-RAD1-HUS1 complex in meiotic chromosome maintenance". PLOS Genetics. 9 (2): e1003320. doi:10.1371/journal.pgen.1003320. PMC 3585019. PMID 23468651.
  9. ↑ Pereira C, Arroyo-Martinez GA, Guo MZ, Downey MS, Kelly ER, Grive KJ, et al. (February 2022). "Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosis". eLife. 11. doi:10.7554/eLife.68677. PMC 8824475. PMID 35133274.
  10. ↑ Cai RL, Yan-Neale Y, Cueto MA, Xu H, Cohen D (Sep 2000). "HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins". The Journal of Biological Chemistry. 275 (36): 27909–16. doi:10.1074/jbc.M000168200. PMID 10846170.
  11. ↑ Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman HB, Pledger WJ, Wang HG (Nov 2000). "PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition". Oncogene. 19 (46): 5291–7. doi:10.1038/sj.onc.1203901. PMID 11077446. S2CID 8931364.
  12. 1 2 Volkmer E, Karnitz LM (Jan 1999). "Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex". The Journal of Biological Chemistry. 274 (2): 567–70. doi:10.1074/jbc.274.2.567. PMID 9872989. S2CID 28787137.
  13. ↑ Hang H, Zhang Y, Dunbrack RL, Wang C, Lieberman HB (Apr 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.
  14. ↑ Bermudez VP, Lindsey-Boltz LA, Cesare AJ, Maniwa Y, Griffith JD, Hurwitz J, Sancar A (Feb 2003). "Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro". Proceedings of the National Academy of Sciences of the United States of America. 100 (4): 1633–8. Bibcode:2003PNAS..100.1633B. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
  15. ↑ Rauen M, Burtelow MA, Dufault VM, Karnitz LM (Sep 2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". The Journal of Biological Chemistry. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID 10884395. S2CID 34505615.
  16. ↑ 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.
  17. ↑ 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". The Journal of Biological Chemistry. 277 (18): 15233–6. doi:10.1074/jbc.C200129200. PMID 11907025. S2CID 24820773.
  18. ↑ Hirai I, Wang HG (Jul 2002). "A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex". The Journal of Biological Chemistry. 277 (28): 25722–7. doi:10.1074/jbc.M203079200. PMID 11994305. S2CID 35202138.

Further reading

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