DCLRE1C

DCLRE1C
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases DCLRE1C, A-SCID, DCLREC1C, RS-SCID, SCIDA, SNM1C, DNA cross-link repair 1C
External IDs MGI: 2441769 HomoloGene: 32547 GeneCards: DCLRE1C
RNA expression pattern


More reference expression data
Orthologs
Species Human Mouse
Entrez

64421

227525

Ensembl

ENSG00000152457

ENSMUSG00000026648

UniProt

Q96SD1

Q8K4J0

RefSeq (mRNA)

NM_001110214
NM_146114
NM_175683
NM_001302674
NM_001302684

RefSeq (protein)

NP_001103684.1
NP_001289603.1
NP_001289613.1
NP_666226.2
NP_783614.1

Location (UCSC) Chr 10: 14.9 – 14.95 Mb Chr 2: 3.42 – 3.46 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Protein artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene.[3][4]

Function

This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. The protein has endonuclease activity on 5' and 3' overhangs and hairpins when complexed with PRKDC.[5]

Immune response

Artemis plays an essential role in V(D)J recombination, the process by which B cell antibody genes and T cell receptor genes are assembled from individual V (variable), D (diversity), and J (joining) segments.[6] For example, in joining a V segment to a D segment, the RAG (recombination activating gene) nuclease cuts both DNA strands adjacent to a V segment and adjacent to a D segment. The intervening DNA between the V and D segments is ligated to form a circular DNA molecule that is lost from the chromosome. At each of the two remaining ends, called the coding ends, the two strands of DNA are joined to form a hairpin structure. Artemis nuclease, in a complex with the DNA-dependent protein kinase (DNA‑PK), binds to these DNA ends and makes a single cut near the tip of the hairpin. The exposed 3' termini are subject to deletion and addition of nucleotides by a variety of exonucleases and DNA polymerases, before the V and D segments are ligated to restore the integrity of the chromosome. The exact site of cleavage of the hairpin by Artemis is variable, and this variability, combined with random nucleotide deletion and addition, confers extreme diversity upon the resulting antibody and T-cell receptor genes, thus allowing the immune system to mount an immune response to virtually any foreign antigen.[7] In Artemis-deficient individuals, V(D)J recombination is blocked because the hairpin ends cannot be opened, and so no mature B or T cells are produced, a condition known as severe combined immune deficiency (SCID). Artemis was first identified as the gene defective in a subset of SCID patients that were unusually sensitive to radiation.

Repair of DNA breaks

Cells deficient in Artemis are more sensitive than normal cells to X‑rays[3] and to chemical agents that induce double-strand breaks (DSBs),[8] and they show a higher incidence of chromosome breaks following irradiation.[9] Direct measurement of DSBs by pulsed-field electrophoresis indicates that in Artemis-deficient cells 75-90% of DSBs are repaired rapidly, just as in normal cells. However, the remaining 10-20% of DSBs that are repaired more slowly (2-24 hr) in normal cells, are not repaired at all in Artemis-deficient cells.[10] Repair of these presumably difficult-to-rejoin breaks also requires several other proteins, including the Mre11/Rad50/NBS1 complex, the ataxia telangiectasia-mutated ATM kinase, and 53BP1. Because Artemis can remove damaged ends from DNA,[8] it has been proposed that these DSBs are those whose damaged ends require trimming by Artemis. However, evidence that both ATM and Artemis are specifically required for repair of DSBs in heterochromatin,[11][12] has called this interpretation into question.

Clinical significance

Mutations in this gene cause Athabascan-type severe combined immunodeficiency (SCIDA).[13]

Interactions

DCLRE1C has been shown to interact with DNA-PKcs.[14]

References

  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. 1 2 Moshous D, Callebaut I, de Chasseval R, Corneo B, Cavazzana-Calvo M, Le Deist F, Tezcan I, Sanal O, Bertrand Y, Philippe N, Fischer A, de Villartay JP (May 2001). "Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency". Cell. 105 (2): 177–86. doi:10.1016/S0092-8674(01)00309-9. PMID 11336668.
  4. Li L, Drayna D, Hu D, Hayward A, Gahagan S, Pabst H, Cowan MJ (Mar 1998). "The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p". Am. J. Hum. Genet. 62 (1): 136–44. doi:10.1086/301688. PMC 1376812Freely accessible. PMID 9443881.
  5. "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011.
  6. de Villartay JP (2009). "V(D)J recombination deficiencies". Adv. Exp. Med. Biol. 650: 46–58. doi:10.1007/978-1-4419-0296-2_4. PMID 19731800.
  7. Lu H, Schwarz K, Lieber MR (2007). "Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombination". Nucleic Acids Res. 35 (20): 6917–23. doi:10.1093/nar/gkm823. PMC 2175297Freely accessible. PMID 17932067.
  8. 1 2 Povirk LF, Zhou T, Zhou R, Cowan MJ, Yannone SM (February 2007). "Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease". J. Biol. Chem. 282 (6): 3547–58. doi:10.1074/jbc.M607745200. PMID 17121861.
  9. Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S, Stiff T, Jeggo P, Löbrich M (March 2007). "Chromosome breakage after G2 checkpoint release". J. Cell Biol. 176 (6): 749–55. doi:10.1083/jcb.200612047. PMC 2064048Freely accessible. PMID 17353355.
  10. Riballo E, Kühne M, Rief N, Doherty A, Smith GC, Recio MJ, Reis C, Dahm K, Fricke A, Krempler A, Parker AR, Jackson SP, Gennery A, Jeggo PA, Löbrich M (December 2004). "A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci". Mol. Cell. 16 (5): 715–24. doi:10.1016/j.molcel.2004.10.029. PMID 15574327.
  11. Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M, Jeggo PA (July 2008). "ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin". Mol. Cell. 31 (2): 167–77. doi:10.1016/j.molcel.2008.05.017. PMID 18657500.
  12. Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S, Goodarzi AA, Krempler A, Jeggo PA, Löbrich M (November 2009). "ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2". EMBO J. 28 (21): 3413–27. doi:10.1038/emboj.2009.276. PMC 2752027Freely accessible. PMID 19779458.
  13. "Entrez Gene: DCLRE1C DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae)".
  14. Ma Y, Pannicke U, Schwarz K, Lieber MR (March 2002). "Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination". Cell. 108 (6): 781–94. doi:10.1016/S0092-8674(02)00671-2. PMID 11955432.

Further reading

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