MRE11A
MRE11A
이중스트랜드파손보수단백질 MRE11은 인간에게 MRE11 유전자에 의해 암호화된 효소다.[5]이 유전자는 MRE11A로 지정되어 오늘날 MRE11P1로 명명된 유사유전자 MRE11B와 구별된다.
함수
이 유전자는 동질 재조합, 말단소립 길이 유지, DNA 이중 가닥 파괴 수리에 관여하는 핵 단백질을 암호화하고 있다.단백질 자체로는 3~5'의 엑소누클레스 활동과 엔도누클레스 활동이 있다.단백질은 RAD50 호몰로겐 콤플렉스를 형성한다. 이 콤플렉스는 DNA의 비호몰로 접합에 필요하며 단일 가닥의 DNA 내분비절제 및 3'에서 5'까지의 외분비절제 활동을 가지고 있다.이 단백질은 DNA 리게아제와 결합하여 DNA 조각의 끝부분 근처에 있는 짧은 호몰로지를 사용하여 체외에서 비완성 종말의 결합을 촉진한다.이 유전자는 3번 염색체에 유사 유전자를 가지고 있다.이 유전자의 대체적인 스플라이싱은 서로 다른 이소 형태를 인코딩하는 두 가지 대본 변형을 초래한다.[6]
직교체
인간 MRE11의 직교자인 Mre11은 프로카리오테의 고고학자 설포오부스 산도칼다리우스에서 발생한다.[7]이 유기체에서 Mre11 단백질은 Rad50 단백질과 상호작용하며 감마선에 의해 실험적으로 도입된 DNA 손상 복구에 적극적인 역할을 하는 것으로 보인다.[7]마찬가지로 진핵 양성자 테트라히메나 Mre11의 감수분열 중 DNA 손상, 이 경우 균질 재조합이 수반될 가능성이 있는 프로세스에 의해 이중 가닥이 깨지는 수리를 위해 필요하다.[8]이러한 관찰은 인간 MRE11이 DNA 손상을 복구하는 초기 과정에 역할을 했던 원핵 및 원생 조상 Mre11 단백질의 후손임을 시사한다.
암에서의 과다압박동
MRE11은 이중 Strand Break의 MMEJ(Microhomology-mediated End Connection) 수리에 대한 역할을 한다.이 오류에 취약한 DNA 수리 경로에 필요한 6가지 효소 중 하나이다.[9]MRE11은 유방암에서 과잉진압을 받는다.[10]
암은 한 개 이상의 DNA 수리 유전자의 발현이 매우 부족한 경우가 많지만, DNA 수리 유전자의 과다 발현이 암에서는 보통이 아니다.예를 들어 세균선 세포에 돌연변이로 결함이 있는 경우 최소 36개의 DNA 수리 효소가 암 위험(계속암 신드롬)을 증가시킨다.[citation needed](DNA 복구결핍장애도 본다.)이와 유사하게, 적어도 12개의 DNA 수리 유전자가 하나 이상의 암에서 후생적으로 억제되는 것이 자주 발견되었다.([citation needed]후생적으로 감소된 DNA 수리 및 암 참조)일반적으로 DNA 수리 효소의 불충분한 표현은 복제 오류(변환 합성)를 통해 돌연변이와 암을 유발하는 비복제 DNA 손상을 증가시킨다.그러나 MRE11 매개 MMEJ 수리는 부정확성이 매우 높기 때문에 이 경우 저표현보다는 과표현상이 암으로 이어지는 것으로 보인다.
상호작용
MRE11은 다음과 상호 작용하는 것으로 나타났다.
- ATM,[11][12]
- BRCA1,[12][13][14][15]
- Ku70,[16]
- MDC1,[17]
- NBN,[12][18][19][20][21]
- Rad50,[12][13][16][18][22] 그리고
- TERF2.[23]
참고 항목
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG000020922 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000031928 - 앙상블, 2017년 5월
- ^ "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.
- ^ Petrini JH, Walsh ME, DiMare C, Chen XN, Korenberg JR, Weaver DT (September 1995). "Isolation and characterization of the human MRE11 homologue". Genomics. 29 (1): 80–6. doi:10.1006/geno.1995.1217. PMID 8530104.
- ^ "Entrez Gene: MRE11 MRE11 meiotic recombination 11 homolog A (S. cerevisiae)".
- ^ a b Quaiser A, Constantinesco F, White MF, Forterre P, Elie C (February 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 Molecular Biology. 9: 25. doi:10.1186/1471-2199-9-25. PMC 2288612. PMID 18294364.
- ^ 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. doi:10.1007/s00412-010-0274-9. PMID 20422424. S2CID 12642689.
- ^ Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (March 2015). "Homology and enzymatic requirements of microhomology-dependent alternative end joining". Cell Death & Disease. 6 (3): e1697. doi:10.1038/cddis.2015.58. PMC 4385936. PMID 25789972.
- ^ Yuan SS, Hou MF, Hsieh YC, Huang CY, Lee YC, Chen YJ, Lo S (October 2012). "Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer". Journal of the National Cancer Institute. 104 (19): 1485–502. doi:10.1093/jnci/djs355. PMID 22914783.
- ^ Kim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". The Journal of Biological Chemistry. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
- ^ a b c d Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes & Development. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC 316544. PMID 10783165.
- ^ a b Chiba N, Parvin JD (October 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". The Journal of Biological Chemistry. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724.
- ^ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
- ^ Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, et al. (July 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science. 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999.
- ^ a b Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (October 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics. 23 (2): 194–8. doi:10.1038/13821. PMID 10508516. S2CID 13443404.
- ^ Xu X, Stern DF (October 2003). "NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors". FASEB Journal. 17 (13): 1842–8. doi:10.1096/fj.03-0310com. PMID 14519663. S2CID 24870579.
- ^ a b Trujillo KM, Yuan SS, Lee EY, Sung P (August 1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". The Journal of Biological Chemistry. 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. PMID 9705271.
- ^ Cerosaletti KM, Concannon P (June 2003). "Nibrin forkhead-associated domain and breast cancer C-terminal domain are both required for nuclear focus formation and phosphorylation". The Journal of Biological Chemistry. 278 (24): 21944–51. doi:10.1074/jbc.M211689200. PMID 12679336.
- ^ Matsuzaki K, Shinohara A, Shinohara M (May 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. doi:10.1534/genetics.107.079236. PMC 2390601. PMID 18458108.
- ^ Desai-Mehta A, Cerosaletti KM, Concannon P (March 2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Molecular and Cellular Biology. 21 (6): 2184–91. doi:10.1128/MCB.21.6.2184-2191.2001. PMC 86852. PMID 11238951.
- ^ Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (September 1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Molecular and Cellular Biology. 16 (9): 4832–41. doi:10.1128/MCB.16.9.4832. PMC 231485. PMID 8756642.
- ^ 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. S2CID 6689794.
추가 읽기
- Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JH (September 1996). "Human Rad50 is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombinational DNA repair". Molecular and Cellular Biology. 16 (9): 4832–41. doi:10.1128/MCB.16.9.4832. PMC 231485. PMID 8756642.
- Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR, et al. (May 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. doi:10.1016/S0092-8674(00)81175-7. PMID 9590181. S2CID 14548642.
- Paull TT, Gellert M (June 1998). "The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks". Molecular Cell. 1 (7): 969–79. doi:10.1016/S1097-2765(00)80097-0. PMID 9651580.
- Trujillo KM, Yuan SS, Lee EY, Sung P (August 1998). "Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95". The Journal of Biological Chemistry. 273 (34): 21447–50. doi:10.1074/jbc.273.34.21447. PMID 9705271.
- Chamankhah M, Wei YF, Xiao W (December 1998). "Isolation of hMRE11B: failure to complement yeast mre11 defects due to species-specific protein interactions". Gene. 225 (1–2): 107–16. doi:10.1016/S0378-1119(98)00530-7. PMID 9931460.
- Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, et al. (July 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science. 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999.
- Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (October 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics. 23 (2): 194–8. doi:10.1038/13821. PMID 10508516. S2CID 13443404.
- Kim ST, Lim DS, Canman CE, Kastan MB (December 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". The Journal of Biological Chemistry. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
- Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, et al. (December 1999). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder". Cell. 99 (6): 577–87. doi:10.1016/S0092-8674(00)81547-0. PMID 10612394. S2CID 14434655.
- Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (April 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes & Development. 14 (8): 927–39. doi:10.1101/gad.14.8.927. PMC 316544. PMID 10783165.
- Gatei M, Young D, Cerosaletti KM, Desai-Mehta A, Spring K, Kozlov S, et al. (May 2000). "ATM-dependent phosphorylation of nibrin in response to radiation exposure". Nature Genetics. 25 (1): 115–9. doi:10.1038/75508. PMID 10802669. S2CID 23521589.
- 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. S2CID 6689794.
- de Vries H, Rüegsegger U, Hübner W, Friedlein A, Langen H, Keller W (November 2000). "Human pre-mRNA cleavage factor II(m) contains homologs of yeast proteins and bridges two other cleavage factors". The EMBO Journal. 19 (21): 5895–904. doi:10.1093/emboj/19.21.5895. PMC 305781. PMID 11060040.
- Fukuda T, Sumiyoshi T, Takahashi M, Kataoka T, Asahara T, Inui H, et al. (January 2001). "Alterations of the double-strand break repair gene MRE11 in cancer". Cancer Research. 61 (1): 23–6. PMID 11196167.
- Desai-Mehta A, Cerosaletti KM, Concannon P (March 2001). "Distinct functional domains of nibrin mediate Mre11 binding, focus formation, and nuclear localization". Molecular and Cellular Biology. 21 (6): 2184–91. doi:10.1128/MCB.21.6.2184-2191.2001. PMC 86852. PMID 11238951.
- Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (May 2001). "Direct DNA binding by Brca1". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
- Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA (May 2001). "Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase". Cell. 105 (4): 473–85. doi:10.1016/S0092-8674(01)00335-X. PMID 11371344. S2CID 15913630.
- Pitts SA, Kullar HS, Stankovic T, Stewart GS, Last JI, Bedenham T, et al. (May 2001). "hMRE11: genomic structure and a null mutation identified in a transcript protected from nonsense-mediated mRNA decay". Human Molecular Genetics. 10 (11): 1155–62. doi:10.1093/hmg/10.11.1155. PMID 11371508.
- Chiba N, Parvin JD (October 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". The Journal of Biological Chemistry. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724.
- Beikzadeh M, Latham MP (October 2020). "The dynamic nature of the Mre11-Rad50 DNA break repair complex". Progress in Biophysics and Molecular Biology. 163: 14–22. doi:10.1016/j.pbiomolbio.2020.10.007. PMC 8065065. PMID 33121960.
