Ver o código fonte de "Artemis (proteína)"

{{Xene-proteína
|nome           = DCLRE1C
|nomes          = A-SCID, DCLREC1C, RS-SCID, SCIDA, SNM1C, DNA cross-link repair 1C
|imaxe           = DCLRE1C.png
|imaxe_tamaño    = 
|imaxe_pé       = 
|HGNCid           =17642
|MGIid            = 2441769
|símbolo          = DCLRE1C
|símbolos_alt     = A-SCID, DCLREC1C, RS-SCID, SCIDA, SNM1C, DNA cross-link repair 1C
<!-- Datos xenéticos -->
|Xene              = DCLRE1C
|Xene_tipo         = codificante de proteínas
|Cromosoma        = 10
|Brazo            = p
|Banda            = 13
|LocusSupplementaryData = 
<!-- Estrutura/función proteica -->
|Longo_proteína   = 
|Peso_molecular   = 
|Estrutura       = 
|Tipo             = 
|Funcións        = 
|Dominio          = 
|Motivo           = 
|Produtos_alt    = 
|Función         =
|Compoñente        =
|Proceso          =
<!-- Info adicional -->
|Taxon            = 
|Célula           = 
|Localización        = 
|Modificación     = 
|Ruta             = 
|Interaccións    = 
|Prop_biofisicas  = 
<!-- Datos encimáticos -->
|Act_catalítica   = 
|Cofactores       = 
|Reg_encimática   = 
|Km               = 
|Vmax             = 
<!-- Datos do receptor/ligando -->
|Acción           = 
|Agonista         = 
|Antagonista      = 
<!-- Datos biotecnolóxicos/médicos -->
|Enfermidade       = 
|Fármaco          = 
|Biotecnoloxía    = 
<!-- Bases de datos -->
|Accesión         = 
|ECnumber         = 
|ATC_prefix       = 
|ATC_suffix       = 
|ATC_supplemental = 
|CAS_number       = 
|CAS_supplemental = 
|DrugBank         =
|Homologene       = 32547
|IUPHAR           =
|OMIM             = 605988
|GeneAtlas_image1 =PBB GE DCLRE1C 222233 s at fs.png
|GeneAtlas_image2 =PBB GE DCLRE1C 219678 x at fs.png
|GeneAtlas_image3 =
|PDB              = 
|Varios_PDB       ={{PDB2|3W1B}}, {{PDB2|3W1G}}, {{PDB2|4HTP}}
|NCBI             =
|KEGG             =
|Orthologs =
<!-- Ortoloxía -->
|Hs_EntrezGene =64421
|Hs_Ensembl =ENSG00000152457
|Hs_RefseqmRNA =NM_001033
|Hs_RefseqProtein =NP_001029
|Hs_GenLoc_db =hg10
|Hs_GenLoc_chr = 10
|Hs_GenLoc_start =	14897359
|Hs_GenLoc_end =14954432
|Hs_Uniprot =Q96SD1
|Mm_EntrezGene = 227525
|Mm_Ensembl = ENSMUSG00000026648
|Mm_RefseqmRNA = NM_001110214
|Mm_RefseqProtein = NP_001103684
|Mm_GenLoc_db = mm9
|Mm_GenLoc_chr = 2
|Mm_GenLoc_start = 3425168
|Mm_GenLoc_end = 3465167
|Mm_Uniprot = Q8K4J0
<!-- Info relacionada -->
|Artigo         = 
|Publicación      = 
}}
'''Artemis''' ou Ártemis é unha [[proteína]] que nos humanos está codificada no [[xene]] '''''DCLRE1C'''''  (do inglés ''<u>D</u>NA <u>c</u>ross-<u>l</u>ink <u>re</u>pair <u>1C</u>'') do [[cromosoma 10]].<ref name="pmid11336668">{{cite journal | vauthors = 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 | title = Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency | journal = Cell | volume = 105 | issue = 2 | pages = 177–86  | date = maio de 2001 | pmid = 11336668 | doi = 10.1016/S0092-8674(01)00309-9 | hdl = 11655/13789  }}</ref><ref name="pmid9443881">{{cite journal | vauthors = Li L, Drayna D, Hu D, Hayward A, Gahagan S, Pabst H, Cowan MJ | title = The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p | journal = Am. J. Hum. Genet. | volume = 62 | issue = 1 | pages = 136–44  | date = Mar 1998 | pmid = 9443881 | pmc = 1376812 | doi = 10.1086/301688 }}</ref>

== Función ==
Artemis é unha [[proteína nuclear]] que intervén na [[recombinación V(D)J]] e na [[reparación do ADN]]. A proteína ten actividade de [[endonuclease]] nas partes que sobresaen 5' e 3' do ADN e nas forquitas de ADN cando está en complexo con [[DNA-PKcs|PRKDC]].<ref name="UniProtKB">{{cite web | title = Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)| url = https://www.uniprot.org/uniprot/Q96SD1| access-date = 2 de xuño de 2011}}</ref>

=== Resposta inmune ===

Artemis exerce un papel esencial na [[recombinación V(D)J]], o proceso polo cal os xenes dos [[anticorpo]]s producidos polas [[célula B|células B]] e os xenes do [[receptor de célula T]] se ensamblan a partir de segmentos xénicos individuais V (variable), D (de diversidade), e J (de unión, ''joining'' en inglés).<ref name="pmid19731800">{{cite book | vauthors = de Villartay JP | title = V(D)J recombination deficiencies | volume = 650 | pages = 46–58 | year = 2009 | pmid = 19731800 | doi = 10.1007/978-1-4419-0296-2_4 | series = Advances in Experimental Medicine and Biology | isbn = 978-1-4419-0295-5 }}</ref> Por exemplo, na unión dun segmento V cun segmento D, a [[xene activador da recombinación|nulcease RAG (xene activador da recombinación)]] corta ambas as febras do [[ADN]] adxacentes a un segmento V e adxacentes a un segmento D.  O ADN intercalado entre os segmentos V e D lígase para formar unha molécula de ADN circular que se perde do [[cromosoma]]. En cada un dos dous extremos restantes, chamados extremos codificantes, as dúas febras do ADN únense para formar unha estrutura en forquita. A nuclease Artemis, en complexo coa proteína quinase dependente de ADN ([[DNA‑PK]]), únese a estes extremos do ADN e fai un só corte preto do extremo da forquita. Os extremos terminais 3' expostos son sometidos a eliminación e adición de [[nucleótido]]s por unha variedade de [[exonuclease]]s e [[ADN polimerase]]s, antes de que os segmentos V e D sexan ligados para restaurar a integridade do cromosoma. O sitio exacto de corte da forquita por Artemis é variable, e esta variabilidade, combinada coa eliminación e adición de nucleótidos, proporciona unha enorme diversidadade aos xenes resultantes dos anticorpos e dos receptors de células T, o que permite que o sistema inmune teña a capacidade de organizar unha resposta inmunitaria contra virtuamente calquera [[antíxeno]] alleo.<ref name="pmid17932067">{{cite journal | vauthors = Lu H, Schwarz K, Lieber MR | title = Extent to which hairpin opening by the Artemis:DNA-PKcs complex can contribute to junctional diversity in V(D)J recombination | journal = Nucleic Acids Res. | volume = 35 | issue = 20 | pages = 6917–23 | year = 2007 | pmid = 17932067 | pmc = 2175297 | doi = 10.1093/nar/gkm823 }}</ref> En individuos con deficiencia de Artemis, a recombinación V(D)J queda bloqueada porque os extremos da forquita non se poden abrir, e así non se produce ningunha célula B ou T madura, unha condición chamada [[inmunodeficiencia combinada grave]].  Artemis foi identificada primeiramente como o xene defectivo nun conxunto de pacientes con esta deficiencia inmunitaria que de forma pouco usual eran sensibles á [[radiación]].

=== Reparación de roturas no ADN ===

As células deficientes en Artemis son máis sensibles que as células normais aos [[raios X]]<ref name="pmid11336668" /> e a axentes químicos que inducen [[reparación do ADN#Roturas de dobre febra|roturas de dobre febra]],<ref name=pmid17121861>{{cite journal | vauthors = Povirk LF, Zhou T, Zhou R, Cowan MJ, Yannone SM | title = Processing of 3'-phosphoglycolate-terminated DNA double strand breaks by Artemis nuclease | journal = J. Biol. Chem. | volume = 282 | issue = 6 | pages = 3547–58  | date = febreiro de 2007 | pmid = 17121861 | doi = 10.1074/jbc.M607745200 }}</ref> e mostran unha incidencia máis alta de roturas de cromosomas despois dunha irradiación.<ref name=pmid17353355>{{cite journal | vauthors = Deckbar D, Birraux J, Krempler A, Tchouandong L, Beucher A, Walker S, Stiff T, Jeggo P, Löbrich M | title = Chromosome breakage after G2 checkpoint release | journal = J. Cell Biol. | volume = 176 | issue = 6 | pages = 749–55  | date = marzo de 2007 | pmid = 17353355 | pmc = 2064048 | doi = 10.1083/jcb.200612047 | url = http://sro.sussex.ac.uk/1851/1/deckbar_2007.pdf }}</ref> A medida directa das roturas de dobre febra por [[electroforese de campo pulsado]] indica que en células deficientes en Artemis se reparan o 75-90 % das roturas de dobre febra rapidamente, igual que nas células normais. Porén, o restante 10-20 % das roturas de dobre febra que son reparadas máis de vagar (tardan 2-24 horas) en células normais, non son reparadas en absoluto en células deficientes en Artemis.<ref name=pmid15574327>{{cite journal | vauthors = 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 | title = A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci | journal = Mol. Cell | volume = 16 | issue = 5 | pages = 715–24  | date = decembro de 2004 | pmid = 15574327 | doi = 10.1016/j.molcel.2004.10.029 }}</ref> A reparación destas roturas que se supón son difíciles de rexuntar tamén require da intervención doutras proteínas, como o complexo Mre11/Rad50/NBS1, a [[quinase]] [[serina/treonina quinase aTM|ataxia telanxiectasia mutada]] ATM, e 53BP1. Como Artemis pode eliminar os extremos danados do ADN,<ref name="pmid17121861"/> propúxose que estas roturas de dobre febra a reparar son aquelas cuxos extremos danados requiren ser recortadas por Artemis. Porén, a existencia de evidencias de que tanto a ATM coma Artemis son necesarias especificamente para reparar as roturas de dobre febra na [[heterocromatina]],<ref name=pmid18657500>{{cite journal | vauthors = Goodarzi AA, Noon AT, Deckbar D, Ziv Y, Shiloh Y, Löbrich M, Jeggo PA | title = ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin | journal = Mol. Cell | volume = 31 | issue = 2 | pages = 167–77  | date = xullo de 2008 | pmid = 18657500 | doi = 10.1016/j.molcel.2008.05.017  }}</ref><ref name=pmid19779458>{{cite journal | vauthors = Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S, Goodarzi AA, Krempler A, Jeggo PA, Löbrich M | title = ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2 | journal = EMBO J. | volume = 28 | issue = 21 | pages = 3413–27  | date = novembro de 2009 | pmid = 19779458 | pmc = 2752027 | doi = 10.1038/emboj.2009.276 }}</ref> puxo en dúbida esta interpretación.

Artemis funciona na reparación das [[rotura de dobre febra|roturas de dobre febra]] do ADN que se orixinan por reaccións oxidativas ou por reacción endóxenas.<ref name="pmid21596788">{{cite journal |vauthors=Woodbine L, Brunton H, Goodarzi AA, Shibata A, Jeggo PA |title=Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair |journal=Nucleic Acids Res. |volume=39 |issue=16 |pages=6986–97 |year=2011 |pmid=21596788 |pmc=3167608 |doi=10.1093/nar/gkr331 }}</ref> Dita [[reparación do ADN]] occorre na heterocromatina e na [[eucromatina]].

== Importancia clínica ==
As [[mutación]]s neste xene causan a [[inmunodeficiencia combinada grave]] de tipo Athabasca.<ref name="entrez">{{cite web | title = Entrez Gene: DCLRE1C DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=64421}}</ref>

== Interaccións ==
Esta proteína presenta [[interacción proteína-proteína|interaccións]] con [[DNA-PKcs]].<ref name="pmid11955432">{{cite journal | vauthors = Ma Y, Pannicke U, Schwarz K, Lieber MR | title = Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination | journal = Cell | volume = 108 | issue = 6 | pages = 781–94  | date = marzo de 2002 | pmid = 11955432 | doi = 10.1016/S0092-8674(02)00671-2 }}</ref>

== Notas ==
{{listaref|35em}}

== Véxase tamén ==
=== Bibliografía ===
{{refbegin|35em}}
* {{cite journal | vauthors = Dudásová Z, Chovanec M | title = Artemis, a novel guardian of the genome | journal = Neoplasma | volume = 50 | issue = 5 | pages = 311–8 | year = 2003 | pmid = 14628082 }}
* {{cite journal | vauthors = Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O | title = Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence | journal = Nature | volume = 377 | issue = 6547 Suppl | pages = 3–174 | year = 1995 | pmid = 7566098 | doi = <!-- none available --> | url = http://www.columbia.edu/itc/biology/pollack/w4065/client_edit/readings/nature377_3.pdf }}
* {{cite journal | vauthors = Wood RD, Mitchell M, Sgouros J, Lindahl T | title = Human DNA repair genes | journal = Science | volume = 291 | issue = 5507 | pages = 1284–9 | year = 2001 | pmid = 11181991 | doi = 10.1126/science.1056154 | bibcode = 2001Sci...291.1284W   }}
* {{cite journal | vauthors = Ma Y, Pannicke U, Schwarz K, Lieber MR | title = Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination | journal = Cell | volume = 108 | issue = 6 | pages = 781–94 | year = 2002 | pmid = 11955432 | doi = 10.1016/S0092-8674(02)00671-2  }}
* {{cite journal | vauthors = Li L, Moshous D, Zhou Y, Wang J, Xie G, Salido E, Hu D, de Villartay JP, Cowan MJ | title = A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans | journal = J. Immunol. | volume = 168 | issue = 12 | pages = 6323–9 | year = 2002 | pmid = 12055248 | doi = 10.4049/jimmunol.168.12.6323  }}
* {{cite journal | vauthors = Callebaut I, Moshous D, Mornon JP, de Villartay JP | title = Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family | journal = Nucleic Acids Res. | volume = 30 | issue = 16 | pages = 3592–601 | year = 2002 | pmid = 12177301 | pmc = 134238 | doi = 10.1093/nar/gkf470 }}
* {{cite journal | vauthors = 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 | title = Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow | journal = Blood | volume = 101 | issue = 4 | pages = 1446–52 | year = 2003 | pmid = 12406895 | doi = 10.1182/blood-2002-01-0187 | url = http://repub.eur.nl/pub/8235  | hdl = 1765/8235  }}
* {{cite journal | vauthors = 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 | title = Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis | journal = J. Clin. Invest. | volume = 111 | issue = 3 | pages = 381–7 | year = 2003 | pmid = 12569164 | pmc = 151863 | doi = 10.1172/JCI16774 }}
* {{cite journal | vauthors = Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A | title = Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families | journal = Hum. Genet. | volume = 112 | issue = 4 | pages = 348–52 | year = 2003 | pmid = 12592555 | doi = 10.1007/s00439-002-0897-x  }}
* {{cite journal | vauthors = Kobayashi N, Agematsu K, Nagumo H, Yasui K, Katsuyama Y, Yoshizawa K, Ota M, Yachie A, Komiyama A | title = 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 | journal = Clin. Immunol. | volume = 108 | issue = 2 | pages = 159–66 | year = 2003 | pmid = 12921762 | doi = 10.1016/S1521-6616(03)00095-0 }}
* {{cite journal | vauthors = Poinsignon C, Moshous D, Callebaut I, de Chasseval R, Villey I, de Villartay JP | title = The metallo-beta-lactamase/beta-CASP domain of Artemis constitutes the catalytic core for V(D)J recombination | journal = J. Exp. Med. | volume = 199 | issue = 3 | pages = 315–21 | year = 2004 | pmid = 14744996 | pmc = 2211804 | doi = 10.1084/jem.20031142 }}
* {{cite journal | vauthors = Pannicke U, Ma Y, Hopfner KP, Niewolik D, Lieber MR, Schwarz K | title = Functional and biochemical dissection of the structure-specific nuclease ARTEMIS | journal = EMBO J. | volume = 23 | issue = 9 | pages = 1987–97 | year = 2004 | pmid = 15071507 | pmc = 404326 | doi = 10.1038/sj.emboj.7600206 }}
* {{cite journal | vauthors = Zhang X, Succi J, Feng Z, Prithivirajsingh S, Story MD, Legerski RJ | title = Artemis is a phosphorylation target of ATM and ATR and is involved in the G2/M DNA damage checkpoint response | journal = Mol. Cell. Biol. | volume = 24 | issue = 20 | pages = 9207–20 | year = 2004 | pmid = 15456891 | pmc = 517881 | doi = 10.1128/MCB.24.20.9207-9220.2004 }}
* {{cite journal | vauthors = Poinsignon C, de Chasseval R, Soubeyrand S, Moshous D, Fischer A, Haché RJ, de Villartay JP | title = Phosphorylation of Artemis following irradiation-induced DNA damage | journal = Eur. J. Immunol. | volume = 34 | issue = 11 | pages = 3146–55 | year = 2004 | pmid = 15468306 | doi = 10.1002/eji.200425455 }}
{{refend}}

=== Ligazóns externas ===
* {{PDBe-KB2|Q96SD1|Protein artemis}}

{{control de autoridades}}
[[Categoría:Proteínas]]