DCLRE1C

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DNA cross-link repair 1C
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DCLRE1C ; A-SCID; DCLREC1C; RS-SCID; SCIDA; SNM1C
External IDs OMIM605988 MGI2441769 HomoloGene32547 GeneCards: DCLRE1C Gene
RNA expression pattern
PBB GE DCLRE1C 219678 x at tn.png
PBB GE DCLRE1C 222233 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 64421 227525
Ensembl ENSG00000152457 ENSMUSG00000026648
UniProt Q96SD1 Q8K4J0
RefSeq (mRNA) NM_001033855 NM_001110214
RefSeq (protein) NP_001029027 NP_001103684
Location (UCSC) Chr 10:
14.94 – 15 Mb
Chr 2:
3.42 – 3.46 Mb
PubMed search [1] [2]

Protein artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene.[1][2]

Function[edit]

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.[3]

Immune response[edit]

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.[4] 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.[5] 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[edit]

Cells deficient in Artemis are more sensitive than normal cells to X‑rays[1] and to chemical agents that induce double-strand breaks (DSBs),[6] and they show a higher incidence of chromosome breaks following irradiation.[7] 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.[8] 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,[6] 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,[9][10] has called this interpretation into question.

Clinical significance[edit]

Mutations in this gene cause Athabascan-type severe combined immunodeficiency (SCIDA).[11]

Interactions[edit]

DCLRE1C has been shown to interact with DNA-PKcs.[12]

References[edit]

  1. ^ a b Moshous D, Callebaut I, de Chasseval R, Corneo B, Cavazzana-Calvo M, Le Deist F et al. (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. 
  2. ^ Li L, Drayna D, Hu D, Hayward A, Gahagan S, Pabst H et al. (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 1376812. PMID 9443881. 
  3. ^ "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011. 
  4. ^ de Villartay JP (2009). "V(D)J recombination deficiencies". Adv. Exp. Med. Biol. 650: 46–58. PMID 19731800. 
  5. ^ 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 2175297. PMID 17932067. 
  6. ^ a b 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. 
  7. ^ Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S et al. (March 2007). "Chromosome breakage after G2 checkpoint release". J. Cell Biol. 176 (6): 749–55. doi:10.1083/jcb.200612047. PMC 2064048. PMID 17353355. 
  8. ^ Riballo E, Kühne M, Rief N, Doherty A, Smith GC, Recio MJ et al. (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.  Vancouver style error (help)
  9. ^ Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M et al. (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.  Vancouver style error (help)
  10. ^ Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S et al. (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 2752027. PMID 19779458. 
  11. ^ "Entrez Gene: DCLRE1C DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae)". 
  12. ^ 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[edit]