HUS1

HUS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3A1J, 3G65, 3GGR
Identifiers
Aliases	HUS1 , hHUS1 checkpoint clamp component
External IDs	OMIM: 603760; MGI: 1277962; HomoloGene: 37932; GeneCards: HUS1; OMA:HUS1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p12.3 Start 47,963,288 bp [1] End 47,979,615 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 A1|11 5.74 cM Start 8,943,137 bp [2] End 8,961,191 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad monocyte sural nerve Achilles tendon islet of Langerhans rectum epithelium of colon muscle of thigh gastrocnemius muscle stromal cell of endometrium Top expressed in secondary oocyte primary oocyte zygote tail of embryo genital tubercle primitive streak substantia nigra proximal tubule ureter abdominal wall More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component site of double-strand break cytoplasm cytosol nucleoplasm checkpoint clamp complex nucleolus nucleus Biological process regulation of protein phosphorylation nucleotide-excision repair meiotic DNA integrity checkpoint signaling embryo development mitotic cell cycle checkpoint signaling mitotic intra-S DNA damage checkpoint signaling negative regulation of DNA replication cellular response to DNA damage stimulus protein phosphorylation mitotic DNA replication checkpoint signaling cellular response to ionizing radiation response to UV double-strand break repair via homologous recombination DNA damage checkpoint signaling DNA repair embryo development ending in birth or egg hatching telomere maintenance DNA replication regulation of signal transduction by p53 class mediator Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 11: 8.94 – 8.96 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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:

• HDAC1, ^[10]
• PCNA, ^[11]
• RAD1 homolog ^{[12] [13]}
• RAD17, ^{[14] [15]} and
• RAD9A. ^{[16] [12] [17] [18]}

References

1. GRCh38: Ensembl release 89: ENSG00000136273 – Ensembl, May 2017
2. 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. 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. 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

• Dominguez O, Ashhab Y, Sabater L, Belloso E, Caro P, Pujol-Borrell R (Dec 1998). "Cloning of ARE-containing genes by AU-motif-directed display". Genomics. 54 (2): 278–86. doi:10.1006/geno.1998.5548. PMID   9828130.
• 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.
• St Onge RP, Udell CM, Casselman R, Davey S (Jun 1999). "The human G2 checkpoint control protein hRAD9 is a nuclear phosphoprotein that forms complexes with hRAD1 and hHUS1". Molecular Biology of the Cell. 10 (6): 1985–95. doi:10.1091/mbc.10.6.1985. PMC   25401 . PMID   10359610.
• Hang H, Lieberman HB (Apr 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 (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.
• Burtelow MA, Kaufmann SH, Karnitz LM (Aug 2000). "Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage". The Journal of Biological Chemistry. 275 (34): 26343–8. doi: 10.1074/jbc.M001244200 . PMID   10852904. S2CID   24638557.
• 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.
• 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.
• Xiang SL, Kumano T, Iwasaki SI, Sun X, Yoshioka K, Yamamoto KC (Oct 2001). "The J domain of Tpr2 regulates its interaction with the proapoptotic and cell-cycle checkpoint protein, Rad9". Biochemical and Biophysical Research Communications. 287 (4): 932–40. doi:10.1006/bbrc.2001.5685. hdl: 2297/1794 . PMID   11573955. S2CID   20694221.
• 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.
• Kinzel B, Hall J, Natt F, Weiler J, Cohen D (Mar 2002). "Downregulation of Hus1 by antisense oligonucleotides enhances the sensitivity of human lung carcinoma cells to cisplatin". Cancer. 94 (6): 1808–14. doi: 10.1002/cncr.10383 . PMID   11920544. S2CID   21518094.
• 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.
• Roos-Mattjus P, Vroman BT, Burtelow MA, Rauen M, Eapen AK, Karnitz LM (Nov 2002). "Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event". The Journal of Biological Chemistry. 277 (46): 43809–12. doi: 10.1074/jbc.M207272200 . PMID   12228248. S2CID   24728793.
• 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.
• Hopkins KM, Wang X, Berlin A, Hang H, Thaker HM, Lieberman HB (Sep 2003). "Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue". Cancer Research. 63 (17): 5291–8. PMID   14500360.
• 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.