HUS1

HUS1 checkpoint clamp component
Rendering based on PDB 3A1J​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3A1J​, 3G65​, 3GGR​
Identifiers
Symbols	HUS1 ; hHUS1
External IDs	OMIM: 603760 MGI: 1277962 HomoloGene: 37932 GeneCards: HUS1 Gene
Gene ontology Molecular function • protein binding Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • checkpoint clamp complex • site of double-strand break Biological process • DNA damage checkpoint • double-strand break repair via homologous recombination • regulation of protein phosphorylation • DNA replication • DNA repair • nucleotide-excision repair • protein phosphorylation • cellular response to DNA damage stimulus • negative regulation of DNA replication • response to UV • embryo development • intra-S DNA damage checkpoint • mitotic DNA replication checkpoint • meiotic DNA integrity checkpoint • cellular response to ionizing radiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3364	15574
Ensembl	ENSG00000136273	ENSMUSG00000020413
UniProt	O60921	Q8BQY8
RefSeq (mRNA)	NM_004507	NM_001303532
RefSeq (protein)	NP_004498	NP_001290461
Location (UCSC)	Chr 7: 47.7 – 47.98 Mb	Chr 11: 8.99 – 9.01 Mb
PubMed search

Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene.^[1][2]

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.^[3]

Interactions

HUS1 has been shown to interact with:

• HDAC1,^[4]
• PCNA,^[5]
• RAD1 homolog^[6][7]
• RAD17,^[8][9] and
• RAD9A.^{[10][6][11][12]}

References

1. 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.
2. 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.
3. "Entrez Gene: HUS1 HUS1 checkpoint homolog (S. pombe)".
4. 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.
5. 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.
6. 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. PMID 9872989.
7. 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.
8. 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. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958.
9. 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.
10. 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. PMID 14611806.
11. 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.
12. 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.

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.
• 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.
• 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.
• 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.
• 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. PMID 11573955.
• 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.
• 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.
• 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.
• 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. 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.