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)
End	47,979,615 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	8,961,191 bp
RNA expression pattern
	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
	; ; ; ;
	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
	3364
	15574
	ENSG00000136273
	ENSMUSG00000020413
	O60921
	Q8BQY8
	NM_004507; NM_001363683
	NM_008316; NM_001303532; NM_001303610
	NP_004498; NP_001350612
	NP_001290461; NP_001290539; NP_032342
	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:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000136273 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020413 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ "Entrez Gene: HUS1 HUS1 checkpoint homolog (S. pombe)".
^ ^a ^b ^c 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136273 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9878245-5] 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.

[pmid9524127-6] 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.

[entrez-7] "Entrez Gene: HUS1 HUS1 checkpoint homolog (S. pombe)".

[Lyndaker2013-8] 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.

[pmid35133274-9] 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.

[pmid10846170-10] 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.

[pmid11077446-11] 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.

[pmid9872989-12] 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.

[pmid11944979-13] 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.

[pmid12578958-14] 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.

[pmid10884395-15] 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.

[pmid14611806-16] 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.

[pmid11907025-17] 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.

[pmid11994305-18] 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.

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