MRN複合体とは - わかりやすく解説 Weblio辞書

MRN複合体

出典: フリー百科事典『ウィキペディア（Wikipedia）』 (2022/09/24 09:35 UTC 版)

MRN複合体（MRNふくごうたい、英: MRN complex、酵母ではMRX複合体）は、MRE11、RAD50、NBS1（英語版）（ヒトではNibrin^[1]、酵母ではXrs2とも呼ばれる）から構成されるタンパク質複合体である。真核生物では、MRN/X複合体は相同組換えや非相同末端結合による修復過程に先立って行われる、DNA二本鎖切断修復の開始段階に重要な役割を果たす。MRN複合体はin vitroとin vivoの双方で二本鎖切断部位に強く結合し、非相同末端結合による修復に先立って破壊された末端を固定したり、または相同組換え修復に先立ってDNA末端の削り込み（DNA end resection）を開始したりしている可能性がある。また、MRN複合体はDNA損傷に応答してチェックポイントキナーゼATMの活性化にも関与する^[2]^[3]。MRE11のエンドヌクレアーゼ活性による短い一本鎖オリゴヌクレオチドの産生が、MRN複合体によるATMの活性化に関係していることが示唆されている^[4]。

出典

^ “Atlas of Genetics and Cytogenetics in Oncology and Haematology - NBS1”. 2008年2月12日閲覧。
^ Lee, JH; Paull, TT (Apr 2, 2004). “Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex.”. Science 304 (5667): 93–6. doi:10.1126/science.1091496. PMID 15064416.
^ Lee, JH; Paull, TT (Apr 22, 2005). “ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.”. Science 308 (5721): 551–4. doi:10.1126/science.1108297. PMID 15790808.
^ Jazayeri A, Balestrini A, Garner E, Haber JE, Costanzo V (2008). “Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity”. The EMBO Journal 27 (14): 1953–1962. doi:10.1038/emboj.2008.128. PMC 2453060. PMID 18596698.
^ White, MF (2011). “Homologous recombination in the archaea: the means justify the ends”. Biochem Soc Trans 39 (1): 15–9. doi:10.1042/BST0390015. PMID 21265740.
^ 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. doi:10.1186/1471-2199-9-25. PMC 2288612. PMID 18294364.
^ Lukaszewicz, A; Howard-Till, RA; Novatchkova, M; Mochizuki, K; Loidl, J (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. doi:10.1007/s00412-010-0274-9. PMID 20422424.
^ Lamarche, BJ; Orazio, NI; Weitzman, MD (10 September 2010). “The MRN complex in double-strand break repair and telomere maintenance.”. FEBS Letters 584 (17): 3682–95. doi:10.1016/j.febslet.2010.07.029. PMC 2946096. PMID 20655309.
^ Lukas, Claudia; Falck, Jacob; Bartkova, Jirina; Bartek, Jiri; Lukas, Jiri (24 February 2003). “Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage”. Nature Cell Biology 5 (3): 255–260. doi:10.1038/ncb945. PMID 12598907.
^ ^a ^b Lavin, M F (10 December 2007). “ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks”. Oncogene 26 (56): 7749–7758. doi:10.1038/sj.onc.1210880. PMID 18066087.
^ You, Z; Chahwan, C; Bailis, J; Hunter, T; Russell, P (July 2005). “ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.”. Molecular and Cellular Biology 25 (13): 5363–79. doi:10.1128/MCB.25.13.5363-5379.2005. PMC 1156989. PMID 15964794.
^ Shibata, A; Moiani, D; Arvai, AS; Perry, J; Harding, SM; Genois, MM; Maity, R; van Rossum-Fikkert, S et al. (9 January 2014). “DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities.”. Molecular Cell 53 (1): 7–18. doi:10.1016/j.molcel.2013.11.003. PMC 3909494. PMID 24316220.
^ de Jager, M; van Noort, J; van Gent, DC; Dekker, C; Kanaar, R; Wyman, C (November 2001). “Human Rad50/Mre11 is a flexible complex that can tether DNA ends.”. Molecular Cell 8 (5): 1129–35. doi:10.1016/s1097-2765(01)00381-1. PMID 11741547.
^ Williams, RS; Moncalian, G; Williams, JS; Yamada, Y; Limbo, O; Shin, DS; Groocock, LM; Cahill, D et al. (3 October 2008). “Mre11 dimers coordinate DNA end bridging and nuclease processing in double-strand-break repair.”. Cell 135 (1): 97–109. doi:10.1016/j.cell.2008.08.017. PMC 2681233. PMID 18854158.
^ Zhu, XD; Küster, B; Mann, M; Petrini, JH; de Lange, T (July 2000). “Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres.”. Nature Genetics 25 (3): 347–52. doi:10.1038/77139. PMID 10888888.
^ Ranganathan, V; Heine, WF; Ciccone, DN; Rudolph, KL; Wu, X; Chang, S; Hai, H; Ahearn, IM et al. (26 June 2001). “Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit.”. Current Biology 11 (12): 962–6. doi:10.1016/s0960-9822(01)00267-6. PMID 11448772.
^ Chai, W; Sfeir, AJ; Hoshiyama, H; Shay, JW; Wright, WE (February 2006). “The involvement of the Mre11/Rad50/Nbs1 complex in the generation of G-overhangs at human telomeres.”. EMBO Reports 7 (2): 225–30. doi:10.1038/sj.embor.7400600. PMC 1369251. PMID 16374507.
^ Zhong, ZH; Jiang, WQ; Cesare, AJ; Neumann, AA; Wadhwa, R; Reddel, RR (5 October 2007). “Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres.”. The Journal of Biological Chemistry 282 (40): 29314–22. doi:10.1074/jbc.M701413200. PMID 17693401.
^ “The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder”. Cell 99 (6): 577–87. (1999). doi:10.1016/s0092-8674(00)81547-0. PMID 10612394.
^ “Nijmegen Breakage Syndrome”. GeneReviews. (1993). PMID 20301355.
^ “Human RAD50 deficiency in a Nijmegen Breakage Syndrome-like disorder”. Am J Hum Genet 84 (5): 605–16. (2009). doi:10.1016/j.ajhg.2009.04.010. PMC 2681000. PMID 19409520.
^ “Chromosome instability syndromes”. Nat Rev Dis Primers 5 (1): 64. (2019). doi:10.1038/s41572-019-0113-0. PMID 31537806.
^ Czornak, Kamila; Chughtai, Sanaullah; Chrzanowska, Krystyna H. (December 2008). “Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair”. Journal of Applied Genetics 49 (4): 383–396. doi:10.1007/BF03195638. PMID 19029686.
^ Kavitha, C.V.; Choudhary, Bibha; Raghavan, Sathees C.; Muniyappa, K. (September 2010). “Differential regulation of MRN (Mre11–Rad50–Nbs1) complex subunits and telomerase activity in cancer cells”. Biochemical and Biophysical Research Communications 399 (4): 575–580. doi:10.1016/j.bbrc.2010.07.117. PMID 20682289.
^ Williams, BR; Mirzoeva, OK; Morgan, WF; Lin, J; Dunnick, W; Petrini, JH (16 April 2002). “A murine model of Nijmegen breakage syndrome.”. Current Biology 12 (8): 648–53. doi:10.1016/s0960-9822(02)00763-7. PMID 11967151.
^ Difilippantonio, S; Celeste, A; Fernandez-Capetillo, O; Chen, HT; Reina San Martin, B; Van Laethem, F; Yang, YP; Petukhova, GV et al. (July 2005). “Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models.”. Nature Cell Biology 7 (7): 675–85. doi:10.1038/ncb1270. PMID 15965469. https://zenodo.org/record/1233355.
^ Gładkowska-Dura, M; Dzierzanowska-Fangrat, K; Dura, WT; van Krieken, JH; Chrzanowska, KH; van Dongen, JJ; Langerak, AW (November 2008). “Unique morphological spectrum of lymphomas in Nijmegen breakage syndrome (NBS) patients with high frequency of consecutive lymphoma formation.”. The Journal of Pathology 216 (3): 337–44. doi:10.1002/path.2418. PMID 18788073.
^ Steffen, J; Maneva, G; Popławska, L; Varon, R; Mioduszewska, O; Sperling, K (15 December 2006). “Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation.”. International Journal of Cancer 119 (12): 2970–3. doi:10.1002/ijc.22280. PMID 16998789.
^ ^a ^b Gao, R; Singh, R; Kaul, Z; Kaul, SC; Wadhwa, R (June 2015). “Targeting of DNA Damage Signaling Pathway Induced Senescence and Reduced Migration of Cancer cells.”. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 70 (6): 701–13. doi:10.1093/gerona/glu019. PMID 24747666.
^ Kessenbrock, K; Plaks, V; Werb, Z (2 April 2010). “Matrix metalloproteinases: regulators of the tumor microenvironment.”. Cell 141 (1): 52–67. doi:10.1016/j.cell.2010.03.015. PMC 2862057. PMID 20371345.
^ Voulgari, A; Pintzas, A (December 2009). “Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic.”. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1796 (2): 75–90. doi:10.1016/j.bbcan.2009.03.002. PMID 19306912.
^ Reddel, RR (2014). “Telomere maintenance mechanisms in cancer: clinical implications.”. Current Pharmaceutical Design 20 (41): 6361–74. doi:10.2174/1381612820666140630101047. PMC 4262939. PMID 24975603.
^ Lajud, SA; Nagda, DA; Yamashita, T; Zheng, J; Tanaka, N; Abuzeid, WM; Civantos, A; Bezpalko, O et al. (15 December 2014). “Dual disruption of DNA repair and telomere maintenance for the treatment of head and neck cancer.”. Clinical Cancer Research 20 (24): 6465–78. doi:10.1158/1078-0432.CCR-14-0176. PMID 25324139.
^ Farmer, H; McCabe, N; Lord, CJ; Tutt, AN; Johnson, DA; Richardson, TB; Santarosa, M; Dillon, KJ et al. (14 April 2005). “Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.”. Nature 434 (7035): 917–21. doi:10.1038/nature03445. PMID 15829967.
^ Skvortsov, S; Debbage, P; Lukas, P; Skvortsova, I (April 2015). “Crosstalk between DNA repair and cancer stem cell (CSC) associated intracellular pathways.”. Seminars in Cancer Biology 31: 36–42. doi:10.1016/j.semcancer.2014.06.002. PMID 24954010.
^ Kuroda, S; Urata, Y; Fujiwara, T (2012). “Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: promising targets for radiosensitization.”. Acta Medica Okayama 66 (2): 83–92. PMID 22525466.
^ Chang, F; Lee, JT; Navolanic, PM; Steelman, LS; Shelton, JG; Blalock, WL; Franklin, RA; McCubrey, JA (March 2003). “Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy.”. Leukemia 17 (3): 590–603. doi:10.1038/sj.leu.2402824. PMID 12646949.

「MRN複合体」の続きの解説一覧

MRN複合体のページへのリンク

MRN複合体とは？わかりやすく解説

MRN複合体

「MRN複合体」の関連用語

MRN複合体とは？ わかりやすく解説

MRN複合体

急上昇のことば

「MRN複合体」の関連用語

MRN複合体とは？わかりやすく解説