MRE11A
MRE11A
| |
| Identificadores | |
| Símbolo | MRE11A |
| Símbolos alt. | ATLD, HNGS1, MRE11, MRE11B, MRE11 homólogo A, nuclease de reparación de roturas de dobre febra |
| Entrez | 4361 |
| RefSeq | NP_005581.2 |
| UniProt | P49959 |
| Outros datos | |
| Locus | Cr. 11 :(94.42 – 94.49 Mb) |
A proteína de reparación de roturas de dobre febra no ADN MRE11A é unha proteína que en humanos está codificada no xene MRE11A do cromosoma 11, con función de nuclease.[1]
Función editar
Este xene codifica unha proteína nuclear implicada na recombinación homóloga, mantemento da lonxitude dos telómeros, e reparación das roturas de dobre febra no ADN. A proteína ten de seu unha actividade de exonuclease 3'-5' e de endonuclease. A proteína forma un complexo con RAD50 (o homólogo de Rad50); este complexo cómpre para realizar a unión non homóloga de extremos do ADN e posúe actividades incrementadas de endonuclease de febras simples de ADN e de exonuclease 3' a 5'. En conxunción cunha ADN ligase, esta proteína promove a unión de extremos non complementarios in vitro usando curtas homoloxías preto dos extremos dos fragmentos de ADN. Este xene ten un pseudoxene no cromosoma 3. O empalme alternativo dos transcritos deste xene orixina dúas variantes de transcrición que codifican diferentes isoformas.[2]
Ortólogos de MRE11A editar
Mre11 é un ortólogo do MRE11A humano que aparece na arquea Sulfolobus acidocaldarius.[3] Neste organismo a proteína Mre11 interacciona coa proteína Rad50 e parece ter un papel activo na reparación de danos no ADN introducidos experimentalmente por radiación gamma.[3] De xeito similar, durante a meiose no protista eucariota Tetrahymena Mre11 é necesario para a reparación de danos no ADN, que neste caso son roturas de dobre febra,[4] por medio dun proceso que probablemente implica recombinación homóloga. Estas observacións indican que a MRE11A humana descende de proteínas Mre11 ancestrais de procariotas e protistas, que desempeñaban un papel nos procesos temperáns de repaación dos danos no ADN.
Sobreexpresión de MRE11 no cancro editar
A MRE11 ten un papel na reparación por unión de extremos mediada por microhomoloxía (MMEJ) das roturas de dobre febra. É un dos 6 encimas requiridos para esta vía de reparación do ADN tendente ao erro.[5] A MRE11 é sobreexpresada en cancros de mama.[6]
Os cancros son moi a miúdo deficientes na expresión dun ou máis xenes de reparación do ADN, pero a sobreexpresión dun xene de reparación do ADN é menos usual no cancro. Por exemplo, polo menos 36 encimas de reparación do ADN, cando son mutacionalmente defectuosos en células da liña xerminal, causan un incremento do cancro (síndromes cancerosas hereditarias ou familiares).[7] Igualmente, polo menos 12 xenes de reparación do ADN están frecuentemente reprimidos epixeneticamente nun ou máis cancros.[7] Xeralmente, a expresión deficiente dos encimas de reparación do ADN orixina un incremento de danos no ADN non reparados, os cales, por medio de erros de replicación (síntese translesión), orixinan mutacións e cancro. Porén, a reparación MMEJ mediada por MRE11 é moi inexacta, polo que neste caso, é a sobreexpresión, en troques da subexpresión, a que aparentemente leva a aparición de cancros.
Interaccións editar
MRE11A presenta interaccións con:
Notas editar
- ↑ Petrini JH, Walsh ME, DiMare C, Chen XN, Korenberg JR, Weaver DT (February 1996). "Isolation and characterization of the human MRE11 homologue". Genomics 29 (1): 80–6. PMID 8530104. doi:10.1006/geno.1995.1217.
- ↑ "Entrez Gene: MRE11A MRE11 meiotic recombination 11 homolog A (S. cerevisiae)".
- ↑ 3,0 3,1 Quaiser A, Constantinesco F, White MF, Forterre P, Elie C (2008). "The Mre11 protein interacts with both Rad50 and the HerA bipolar helicase and is recruited to DNA following gamma irradiation in the archaeon Sulfolobus acidocaldarius". BMC Mol. Biol. 9: 25. PMC 2288612. PMID 18294364. doi:10.1186/1471-2199-9-25.
- ↑ Lukaszewicz A, Howard-Till RA, Novatchkova M, Mochizuki K, Loidl J (October 2010). "MRE11 and COM1/SAE2 are required for double-strand break repair and efficient chromosome pairing during meiosis of the protist Tetrahymena". Chromosoma 119 (5): 505–18. PMID 20422424. doi:10.1007/s00412-010-0274-9.
- ↑ Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (2015). "Homology and enzymatic requirements of microhomology-dependent alternative end joining". Cell Death Dis 6: e1697. PMC 4385936. PMID 25789972. doi:10.1038/cddis.2015.58.
- ↑ Yuan SS, Hou MF, Hsieh YC, Huang CY, Lee YC, Chen YJ, Lo S (2012). "Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer". J. Natl. Cancer Inst. 104 (19): 1485–502. PMID 22914783. doi:10.1093/jnci/djs355.
- ↑ 7,0 7,1 Bernstein C, Prasad AR, Nfonsam V, Bernstein H. (2013). DNA Damage, DNA Repair and Cancer, New Research Directions in DNA Repair, Prof. Clark Chen (Ed.), ISBN 978-953-51-1114-6, InTech, http://www.intechopen.com/books/new-research-directions-in-dna-repair/dna-damage-dna-repair-and-cancer
- ↑ Kim ST, Lim DS, Canman CE, Kastan MB (1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. PMID 10608806. doi:10.1074/jbc.274.53.37538.
- ↑ 9,0 9,1 9,2 9,3 Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165. doi:10.1101/gad.14.8.927.
- ↑ 10,0 10,1 Chiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. PMID 11504724. doi:10.1074/jbc.M105227200.
- ↑ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. PMC 33426. PMID 11353843. doi:10.1073/pnas.111125998.
- ↑ Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science 285 (5428): 747–50. PMID 10426999. doi:10.1126/science.285.5428.747.
- ↑ 13,0 13,1 Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nat. Genet. 23 (2): 194–8. PMID 10508516. doi:10.1038/13821.
- ↑ Xu X, Stern DF (2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB J. 17 (13): 1842–8. PMID 14519663. doi:10.1096/fj.03-0310com.
- ↑ 15,0 15,1 Trujillo KM, Yuan SS, Lee EY, Sung P (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". J. Biol. Chem. 273 (34): 21447–50. PMID 9705271. doi:10.1074/jbc.273.34.21447.
- ↑ Cerosaletti KM, Concannon P (2003). "Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation". J. Biol. Chem. 278 (24): 21944–51. PMID 12679336. doi:10.1074/jbc.M211689200.
- ↑ Matsuzaki K, Shinohara A, Shinohara M (2008). "Forkhead-associated domain of yeast Xrs2, a homolog of human Nbs1, promotes nonhomologous end joining through interaction with a ligase IV partner protein, Lif1". Genetics 179 (1): 213–25. PMC 2390601. PMID 18458108. doi:10.1534/genetics.107.079236.
- ↑ Desai-Mehta A, Cerosaletti KM, Concannon P (2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Mol. Cell. Biol. 21 (6): 2184–91. PMC 86852. PMID 11238951. doi:10.1128/MCB.21.6.2184-2191.2001.
- ↑ Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Mol. Cell. Biol. 16 (9): 4832–41. PMC 231485. PMID 8756642.
- ↑ Zhu XD, Küster B, Mann M, Petrini JH, de Lange T (2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres". Nat. Genet. 25 (3): 347–52. PMID 10888888. doi:10.1038/77139.
Véxase tamén editar
Outros artigos editar
Bibliografía editar
- Dolganov GM, Maser RS, Novikov A, et al. (1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair.". Mol. Cell. Biol. 16 (9): 4832–41. PMC 231485. PMID 8756642.
- Carney JP, Maser RS, Olivares H, et al. (1998). "The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.". Cell 93 (3): 477–86. PMID 9590181. doi:10.1016/S0092-8674(00)81175-7.
- Paull TT, Gellert M (1998). "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks.". Mol. Cell 1 (7): 969–79. PMID 9651580. doi:10.1016/S1097-2765(00)80097-0.
- Trujillo KM, Yuan SS, Lee EY, Sung P (1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95.". J. Biol. Chem. 273 (34): 21447–50. PMID 9705271. doi:10.1074/jbc.273.34.21447.
- Chamankhah M, Wei YF, Xiao W (1999). "Isolation of hMRE11B: failure to complement yeast mre11 defects due to species-specific protein interactions.". Gene 225 (1-2): 107–16. PMID 9931460. doi:10.1016/S0378-1119(98)00530-7.
- Zhong Q, Chen CF, Li S, et al. (1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.". Science 285 (5428): 747–50. PMID 10426999. doi:10.1126/science.285.5428.747.
- Goedecke W, Eijpe M, Offenberg HH, et al. (1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis.". Nat. Genet. 23 (2): 194–8. PMID 10508516. doi:10.1038/13821.
- Kim ST, Lim DS, Canman CE, Kastan MB (2000). "Substrate specificities and identification of putative substrates of ATM kinase family members.". J. Biol. Chem. 274 (53): 37538–43. PMID 10608806. doi:10.1074/jbc.274.53.37538.
- Stewart GS, Maser RS, Stankovic T, et al. (2000). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.". Cell 99 (6): 577–87. PMID 10612394. doi:10.1016/S0092-8674(00)81547-0.
- Wang Y, Cortez D, Yazdi P, et al. (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165. doi:10.1101/gad.14.8.927.
- Gatei M, Young D, Cerosaletti KM, et al. (2000). "ATM-dependent phosphorylation of nibrin in response to radiation exposure.". Nat. Genet. 25 (1): 115–9. PMID 10802669. doi:10.1038/75508.
- Zhu XD, Küster B, Mann M, et al. (2000). "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres.". Nat. Genet. 25 (3): 347–52. PMID 10888888. doi:10.1038/77139.
- de Vries H, Rüegsegger U, Hübner W, et al. (2000). "Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors.". EMBO J. 19 (21): 5895–904. PMC 305781. PMID 11060040. doi:10.1093/emboj/19.21.5895.
- Fukuda T, Sumiyoshi T, Takahashi M, et al. (2001). "Alterations of the double-strand break repair gene MRE11 in cancer.". Cancer Res. 61 (1): 23–6. PMID 11196167.
- Desai-Mehta A, Cerosaletti KM, Concannon P (2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization.". Mol. Cell. Biol. 21 (6): 2184–91. PMC 86852. PMID 11238951. doi:10.1128/MCB.21.6.2184-2191.2001.
- Paull TT, Cortez D, Bowers B, et al. (2001). "Direct DNA binding by Brca1.". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. PMC 33426. PMID 11353843. doi:10.1073/pnas.111125998.
- Hopfner KP, Karcher A, Craig L, et al. (2001). "Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase.". Cell 105 (4): 473–85. PMID 11371344. doi:10.1016/S0092-8674(01)00335-X.
- Pitts SA, Kullar HS, Stankovic T, et al. (2001). "hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay.". Hum. Mol. Genet. 10 (11): 1155–62. PMID 11371508. doi:10.1093/hmg/10.11.1155.
- Chiba N, Parvin JD (2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage.". J. Biol. Chem. 276 (42): 38549–54. PMID 11504724. doi:10.1074/jbc.M105227200.