Artemis (protein)
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Artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene.[5][6]
Function
Artemis is 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.[7]
Immune response
Artemis plays an essential role in
Repair of DNA breaks
Cells deficient in Artemis are more sensitive than normal cells to X‑rays[5] and to chemical agents that induce double-strand breaks (DSBs),[10] and they show a higher incidence of chromosome breaks following irradiation.[11] 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.[12] 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,[10] 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,[13][14] has called this interpretation into question.
Artemis functions in the repair of DNA
Clinical significance
Mutations in this gene cause Athabascan-type severe combined immunodeficiency (SCIDA).[16]
Interactions
DCLRE1C has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000152457 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026648 – 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.
- ^ S2CID 12610896.
- PMID 9443881.
- ^ "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011.
- PMID 19731800.
- PMID 17932067.
- ^ PMID 17121861.
- PMID 17353355.
- PMID 15574327.
- PMID 18657500.
- PMID 19779458.
- PMID 21596788.
- ^ "Entrez Gene: DCLRE1C DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae)".
- S2CID 7575525.
Further reading
- Dudásová Z, Chovanec M (2003). "Artemis, a novel guardian of the genome". Neoplasma. 50 (5): 311–8. PMID 14628082.
- Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
- Wood RD, Mitchell M, Sgouros J, Lindahl T (2001). "Human DNA repair genes". Science. 291 (5507): 1284–9. S2CID 17375001.
- Ma Y, Pannicke U, Schwarz K, Lieber MR (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. S2CID 7575525.
- Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, Hu D, de Villartay JP, Cowan MJ (2002). "A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans". J. Immunol. 168 (12): 6323–9. PMID 12055248.
- Callebaut I, Moshous D, Mornon JP, de Villartay JP (2002). "Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family". Nucleic Acids Res. 30 (16): 3592–601. PMID 12177301.
- Noordzij JG, Verkaik NS, van der Burg M, van Veelen LR, de Bruin-Versteeg S, Wiegant W, Vossen JM, Weemaes CM, de Groot R, Zdzienicka MZ, van Gent DC, van Dongen JJ (2003). "Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow". Blood. 101 (4): 1446–52. PMID 12406895.
- Moshous D, Pannetier C, de Chasseval R, le Deist F, Cavazzana-Calvo M, Romana S, Macintyre E, Canioni D, Brousse N, Fischer A, Casanova JL, de Villartay JP (2003). "Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis". J. Clin. Invest. 111 (3): 381–7. PMID 12569164.
- Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A (2003). "Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families". Hum. Genet. 112 (4): 348–52. S2CID 11582061.
- Kobayashi N, Agematsu K, Nagumo H, Yasui K, Katsuyama Y, Yoshizawa K, Ota M, Yachie A, Komiyama A (2003). "Expansion of clonotype-restricted HLA-identical maternal CD4+ T cells in a patient with severe combined immunodeficiency and a homozygous mutation in the Artemis gene". Clin. Immunol. 108 (2): 159–66. PMID 12921762.
- Poinsignon C, Moshous D, Callebaut I, de Chasseval R, Villey I, de Villartay JP (2004). "The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination". J. Exp. Med. 199 (3): 315–21. PMID 14744996.
- Pannicke U, Ma Y, Hopfner KP, Niewolik D, Lieber MR, Schwarz K (2004). "Functional and biochemical dissection of the structure-specific nuclease ARTEMIS". EMBO J. 23 (9): 1987–97. PMID 15071507.
- Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ (2004). "Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response". Mol. Cell. Biol. 24 (20): 9207–20. PMID 15456891.
- Poinsignon C, de Chasseval R, Soubeyrand S, Moshous D, Fischer A, Haché RJ, de Villartay JP (2004). "Phosphorylation of Artemis following irradiation-induced DNA damage". Eur. J. Immunol. 34 (11): 3146–55. PMID 15468306.