HUS1

HUS1 checkpoint homolog (S. pombe)
Rendering based on PDB 3A1J.
Available structures PDB 3A1J, 3G65, 3GGR
Identifiers
Symbols	HUS1; hHUS1
External IDs	OMIM: 603760 MGI: 1277962 HomoloGene: 37932 GeneCards: HUS1 Gene
Gene Ontology Molecular function • protein serine/threonine kinase activity • protein binding Cellular component • nucleus • nucleoplasm • nucleolus • cytoplasm • Golgi apparatus Biological process • cell cycle checkpoint • DNA damage checkpoint • double-strand break repair via homologous recombination • DNA replication • DNA repair • protein phosphorylation • response to DNA damage stimulus • negative regulation of DNA replication • response to UV • embryo development • mitotic cell cycle G1/S transition 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_004507.3	NM_008316.4
RefSeq (protein)	NP_004498.1	NP_032342.1
Location (UCSC)	Chr 7: 47.74 – 48.02 Mb	Chr 11: 8.89 – 8.91 Mb
PubMed search	[1]	[2]

Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene.

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.

Interactions

HUS1 has been shown to interact with RAD9A, RAD17, HDAC1, RAD1 homolog and PCNA.

Further reading

• Dominguez O, Ashhab Y, Sabater L et al (1999). "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 (1999). "Human homologs of Schizosaccharomyces pombe rad1, hus1, and rad9 form a DNA damage-responsive protein complex". J. Biol. Chem. 274 (2): 567–70. doi:10.1074/jbc.274.2.567. PMID 9872989. 
• St Onge RP, Udell CM, Casselman R, Davey S (1999). "The Human G2 Checkpoint Control Protein hRAD9 Is a Nuclear Phosphoprotein That Forms Complexes with hRAD1 and hHUS1". Mol. Biol. Cell 10 (6): 1985–95. PMC 25401. PMID 10359610. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25401. 
• Hang H, Lieberman HB (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 et al (2000). "HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two G2/M checkpoint Rad proteins". J. Biol. Chem. 275 (36): 27909–16. doi:10.1074/jbc.M000168200. PMID 10846170. 
• Burtelow MA, Kaufmann SH, Karnitz LM (2000). "Retention of the human Rad9 checkpoint complex in extraction-resistant nuclear complexes after DNA damage". J. Biol. Chem. 275 (34): 26343–8. doi:10.1074/jbc.M001244200. PMID 10852904. 
• Rauen M, Burtelow MA, Dufault VM, Karnitz LM (2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins hRad1, hHus1, and hRad9". J. Biol. Chem. 275 (38): 29767–71. doi:10.1074/jbc.M005782200. PMID 10884395. 
• Komatsu K, Wharton W, Hang H et al (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 et al (2001). "The J domain of Tpr2 regulates its interaction with the proapoptotic and cell-cycle checkpoint protein, Rad9". Biochem. Biophys. Res. Commun. 287 (4): 932–40. doi:10.1006/bbrc.2001.5685. PMID 11573955. 
• Griffith JD, Lindsey-Boltz LA, Sancar A (2002). "Structures of the human Rad17-replication factor C and checkpoint Rad 9-1-1 complexes visualized by glycerol spray/low voltage microscopy". J. Biol. Chem. 277 (18): 15233–6. doi:10.1074/jbc.C200129200. PMID 11907025. 
• Kinzel B, Hall J, Natt F et al (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 et al (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 et al (2003). "Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event". J. Biol. Chem. 277 (46): 43809–12. doi:10.1074/jbc.M207272200. PMID 12228248. 
• Strausberg RL, Feingold EA, Grouse LH et al (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Bermudez VP, Lindsey-Boltz LA, Cesare AJ et al (2003). "Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro". Proc. Natl. Acad. Sci. U.S.A. 100 (4): 1633–8. doi:10.1073/pnas.0437927100. PMC 149884. PMID 12578958. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149884. 
• Scherer SW, Cheung J, MacDonald JR et al (2003). "Human Chromosome 7: DNA Sequence and Biology". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961. 
• Hopkins KM, Wang X, Berlin A et al (2003). "Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue". Cancer Res. 63 (17): 5291–8. PMID 14500360. 
• Dufault VM, Oestreich AJ, Vroman BT, Karnitz LM (2004). "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.