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维基百科

布盧姆綜合症蛋白

布盧姆綜合症蛋白(Bloom syndrome protein),係一種由BLM基因編碼的人類蛋白質,在布盧姆綜合症患者體內不表達[1]

布盧姆綜合徵蛋白
BLM
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 BLM; BS; RECQ2; RECQL2; RECQL3
扩展标识 遗传学:604610 鼠基因:1328362 同源基因:47902 ChEMBL: 1293237 GeneCards: BLM Gene
EC編號 3.6.4.12
直系同源体
物种 人类 小鼠
Entrez 641 12144
Ensembl ENSG00000197299 ENSMUSG00000030528
UniProt P54132 O88700
mRNA序列 NM_000057 NM_001042527
蛋白序列 NP_000048 NP_001035992
基因位置 Chr 15:
90.72 – 90.82 Mb
Chr 7:
80.45 – 80.54 Mb
PubMed查询 [1] [2]

布盧姆綜合症基因編碼的產物和RecQ英语RecQ家族的DExH盒包含DNA解旋酶有關聯,同時有DNA刺激ATP酶和ATP依賴性DNA解旋酶活性。布盧姆綜合症患者的DNA突變導致布盧姆綜合症蛋白的解旋酶模體損壞或發生改變,可能使得酶失去3'→5'解旋酶活性。正常的布盧姆綜合症蛋白還可能參與對不恰當的同源重組的抑制[2]

減數分裂 编辑

 
一個正常的減數分裂模型,以一個雙鏈DNA分子斷裂開始,緊隨與同源染色體的配對,以及介導重組修復過程的鏈插入過程。對DNA分子的斷裂的修復可以使得交叉互換發生(crossover,縮寫爲C0),也可能使得交叉互換不發生(non-crossover,縮寫爲NCO)。一個名爲「雙霍利迪交叉」(Double Holliday Junction (DHJ))的模型可以概述發生交叉互換的重組(CO)的情況,如右上方所示。不發生交叉互換的重組(NCO)基本可由合成依賴鏈退火(Synthesis Dependent Strand Annealing (SDSA))模型來解釋,如左上方所示。大部分的重組都符合SDSA模型

減數分裂重組通常始於DNA雙鏈的斷裂(DNA double-strand break (DSB))。在重組中,DNA斷裂區的5'端鏈的前段部分會通過一個名爲切除(resection)的過程被切去。在鏈插入的過程中,自由的3'端DNA會插入同源染色體未斷裂的相應區域。在鏈插入後,會通過不同的途徑發生交叉互換發生(crossover,縮寫爲C0)或交叉互換不發生(non-crossover,縮寫爲NCO)的重組(具體可參見條目基因重組)。

芽殖酵母釀酒酵母S.cerevisiae)編碼一種與布盧姆綜合症蛋白同源的蛋白,名爲Sgs1英语Sgs1(小生長抑制物1,Small growth suppressor 1)。Sgs1係一種在同源重組過程中的DNA修復中發揮作用的解旋酶。Sgs1解旋酶可能是釀酒酵母減數分裂過程中的大部分重組事件的調控物質[3]。在正常的減數分裂過程中,Sgs1負責介導交叉互換不發生或發生霍利迪交叉的分子的重組,後一種情況的分子發生的是交叉互換發生的重組[3]

在植物擬南芥A.thaliana)體內,布盧姆綜合症蛋白的同源解旋酶是減數分裂中交叉互換發生的重組進行的主要抑制物[4]。這類解旋酶替換了插入鏈,使得它能與其它的黏性3'端發生退火,通過上述的SDSA過程使得交叉互換不發生的重組發生。根據估計,只有4%的DNA雙鏈斷裂(DSB)以交叉互換發生的重組爲結果[5]。Sequela-Arnaud等人[4]認爲交叉互換發生的重組受限是因爲交叉互換發生的重組(CO)長期成本——交叉互換發生的重組會打亂自然選擇選出的有利的基因。

交互作用 编辑

布盧姆綜合症蛋白可與以下蛋白質發生交互作用

  • 運動失調性毛細血管擴張症突變蛋白英语Ataxia telangiectasia mutated(ATM)[6][7]
  • CHAF1A英语CHAF1A[8]
  • CHEK1英语CHEK1[9]
  • FANCM英语FANCM[10]
  • FEN1英语Flap structure-specific endonuclease 1[11]
  • H2AFX英语H2AFX[9]
  • MLH1英语MLH1[6][12][13][14]
  • P53[9][15][16][17]
  • RAD51L3英语RAD51L3[18]
  • RAD51[19]
  • RPA1英语Replication protein A1[20][21][22]
  • TOP3A英语TOP3A[12][20][23][24]
  • TP53BP1英语TP53BP1[9]
  • WRN英语Werner syndrome ATP-dependent helicase[25]
  • XRCC2英语XRCC2[18]

參考 编辑

  1. ^ Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. January 1998, 272 (49): 30611–4. PMID 9388193. doi:10.1074/jbc.272.49.30611. 
  2. ^ Bloom syndrome. Genetics Home Reference. NIH. [19 March 2013]. (原始内容于2016-07-27). 
  3. ^ 3.0 3.1 De Muyt A, Jessop L, Kolar E, Sourirajan A, Chen J, Dayani Y, Lichten M. BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism. Mol. Cell. 2012, 46 (1): 43–53. PMC 3328772 . PMID 22500736. doi:10.1016/j.molcel.2012.02.020. 
  4. ^ 4.0 4.1 Séguéla-Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, Lemhemdi A, Macaisne N, Van Leene J, Gevaert K, De Jaeger G, Chelysheva L, Mercier R. Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM. Proc. Natl. Acad. Sci. U.S.A. 2015, 112 (15): 4713–8. PMC 4403193 . PMID 25825745. doi:10.1073/pnas.1423107112. 
  5. ^ Crismani, W; Girard, C; Froger, N; Pradillo, M; Santos, JL; Chelysheva, L; et al. FANCM limits meiotic crossovers. Science. 2012, 336 (6088): 1588–90. PMID 22723424. doi:10.1126/science.1220381.  已忽略未知参数|author-name-separator= (帮助); 已忽略未知参数|author-separator= (帮助)
  6. ^ 6.0 6.1 Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. April 2000, 14 (8): 927–39. PMC 316544 . PMID 10783165. doi:10.1101/gad.14.8.927. 
  7. ^ Beamish H, Kedar P, Kaneko H, Chen P, Fukao T, Peng C, Beresten S, Gueven N, Purdie D, Lees-Miller S, Ellis N, Kondo N, Lavin MF. Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM. J. Biol. Chem. August 2002, 277 (34): 30515–23. PMID 12034743. doi:10.1074/jbc.M203801200. 
  8. ^ Jiao R, Bachrati CZ, Pedrazzi G, Kuster P, Petkovic M, Li JL, Egli D, Hickson ID, Stagljar I. Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1. Mol. Cell. Biol. June 2004, 24 (11): 4710–9. PMC 416397 . PMID 15143166. doi:10.1128/MCB.24.11.4710-4719.2004. 
  9. ^ 9.0 9.1 9.2 9.3 Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J. Cell Biol. September 2004, 166 (6): 801–13. PMC 2172115 . PMID 15364958. doi:10.1083/jcb.200405128. 
  10. ^ Deans AJ, West SC. FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia. Mol. Cell. 24 December 2009, 36 (6): 943–53. PMID 20064461. doi:10.1016/j.molcel.2009.12.006. 
  11. ^ Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM. Stimulation of flap endonuclease-1 by the Bloom's syndrome protein. J. Biol. Chem. March 2004, 279 (11): 9847–56. PMID 14688284. doi:10.1074/jbc.M309898200. 
  12. ^ 12.0 12.1 Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP. Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha. Nucleic Acids Res. August 2001, 29 (15): 3172–80. PMC 55826 . PMID 11470874. doi:10.1093/nar/29.15.3172. 
  13. ^ Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K, Kunkel TA, Groden J. The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. J. Biol. Chem. August 2001, 276 (32): 30031–5. PMID 11325959. doi:10.1074/jbc.M009664200. 
  14. ^ Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL, Ryu GH, Freire R, Hickson ID, Jiricny J, Stagljar I. Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1. Nucleic Acids Res. November 2001, 29 (21): 4378–86. PMC 60193 . PMID 11691925. doi:10.1093/nar/29.21.4378. 
  15. ^ Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC. Functional interaction of p53 and BLM DNA helicase in apoptosis. J. Biol. Chem. August 2001, 276 (35): 32948–55. PMID 11399766. doi:10.1074/jbc.M103298200. 
  16. ^ Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV. The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control. Oncogene. December 2001, 20 (57): 8276–80. PMID 11781842. doi:10.1038/sj.onc.1205120. 
  17. ^ Yang Q, Zhang R, Wang XW, Spillare EA, Linke SP, Subramanian D, Griffith JD, Li JL, Hickson ID, Shen JC, Loeb LA, Mazur SJ, Appella E, Brosh RM, Karmakar P, Bohr VA, Harris CC. The processing of Holliday junctions by BLM and WRN helicases is regulated by p53. J. Biol. Chem. August 2002, 277 (35): 31980–7. PMID 12080066. doi:10.1074/jbc.M204111200. 
  18. ^ 18.0 18.1 Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID. Functional interaction between the Bloom's syndrome helicase and the RAD51 paralog, RAD51L3 (RAD51D). J. Biol. Chem. November 2003, 278 (48): 48357–66. PMID 12975363. doi:10.1074/jbc.M308838200. 
  19. ^ Wu L, Davies SL, Levitt NC, Hickson ID. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J. Biol. Chem. June 2001, 276 (22): 19375–81. PMID 11278509. doi:10.1074/jbc.M009471200. 
  20. ^ 20.0 20.1 Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity. J. Biol. Chem. August 2000, 275 (31): 23500–8. PMID 10825162. doi:10.1074/jbc.M001557200. 
  21. ^ Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA. Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J. Biol. Chem. October 2002, 277 (43): 41110–9. PMID 12181313. doi:10.1074/jbc.M205396200. 
  22. ^ Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B. The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination. J. Cell. Sci. April 2002, 115 (Pt 8): 1611–22. PMID 11950880. 
  23. ^ Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID. The Bloom's syndrome gene product interacts with topoisomerase III. J. Biol. Chem. March 2000, 275 (13): 9636–44. PMID 10734115. doi:10.1074/jbc.275.13.9636. 
  24. ^ Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Hum. Mol. Genet. June 2001, 10 (12): 1287–98. PMID 11406610. doi:10.1093/hmg/10.12.1287. 
  25. ^ von Kobbe C, Karmakar P, Dawut L, Opresko P, Zeng X, Brosh RM, Hickson ID, Bohr VA. Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins. J. Biol. Chem. June 2002, 277 (24): 22035–44. PMID 11919194. doi:10.1074/jbc.M200914200. 

拓展閱讀 编辑

  • Woo LL, Onel K, Ellis NA. The broken genome: genetic and pharmacologic approaches to breaking DNA. Ann. Med. 2007, 39 (3): 208–18. PMID 17457718. doi:10.1080/08035250601167136. 
  • McDaniel LD, Schultz RA. Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15. Proc. Natl. Acad. Sci. U.S.A. 1992, 89 (17): 7968–72. PMC 49836 . PMID 1518822. doi:10.1073/pnas.89.17.7968. 
  • Ellis NA, Groden J, Ye TZ, Straughen J, Lennon DJ, Ciocci S, Proytcheva M, German J. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. 1995, 83 (4): 655–66. PMID 7585968. doi:10.1016/0092-8674(95)90105-1. 
  • German J, Roe AM, Leppert MF, Ellis NA. Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. Proc. Natl. Acad. Sci. U.S.A. 1994, 91 (14): 6669–73. PMC 44264 . PMID 8022833. doi:10.1073/pnas.91.14.6669. 
  • Foucault F, Vaury C, Barakat A, Thibout D, Planchon P, Jaulin C, Praz F, Amor-Guéret M. Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom's syndrome. Hum. Mol. Genet. 1998, 6 (9): 1427–34. PMID 9285778. doi:10.1093/hmg/6.9.1427. 
  • Kaneko H, Orii KO, Matsui E, Shimozawa N, Fukao T, Matsumoto T, Shimamoto A, Furuichi Y, Hayakawa S, Kasahara K, Kondo N. BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal. Biochem. Biophys. Res. Commun. 1997, 240 (2): 348–53. PMID 9388480. doi:10.1006/bbrc.1997.7648. 
  • Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID. The Bloom's syndrome gene product interacts with topoisomerase III. J. Biol. Chem. 2000, 275 (13): 9636–44. PMID 10734115. doi:10.1074/jbc.275.13.9636. 
  • Yankiwski V, Marciniak RA, Guarente L, Neff NF. Nuclear structure in normal and Bloom syndrome cells. Proc. Natl. Acad. Sci. U.S.A. 2000, 97 (10): 5214–9. PMC 25808 . PMID 10779560. doi:10.1073/pnas.090525897. 
  • Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000, 14 (8): 927–39. PMC 316544 . PMID 10783165. doi:10.1101/gad.14.8.927. 
  • Karow JK, Constantinou A, Li JL, West SC, Hickson ID. The Bloom's syndrome gene product promotes branch migration of Holliday junctions. Proc. Natl. Acad. Sci. U.S.A. 2000, 97 (12): 6504–8. PMC 18638 . PMID 10823897. doi:10.1073/pnas.100448097. 
  • Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA. Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity. J. Biol. Chem. 2000, 275 (31): 23500–8. PMID 10825162. doi:10.1074/jbc.M001557200. 
  • Dutertre S, Ababou M, Onclercq R, Delic J, Chatton B, Jaulin C, Amor-Guéret M. Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Oncogene. 2000, 19 (23): 2731–8. PMID 10851073. doi:10.1038/sj.onc.1203595. 
  • Barakat A, Ababou M, Onclercq R, Dutertre S, Chadli E, Hda N, Benslimane A, Amor-Guéret M. Identification of a novel BLM missense mutation (2706T>C) in a Moroccan patient with Bloom's syndrome. Hum. Mutat. 2000, 15 (6): 584–5. PMID 10862105. doi:10.1002/1098-1004(200006)15:6<584::AID-HUMU28>3.0.CO;2-I. 
  • Brosh RM, Karow JK, White EJ, Shaw ND, Hickson ID, Bohr VA. Potent inhibition of Werner and Bloom helicases by DNA minor groove binding drugs. Nucleic Acids Res. 2000, 28 (12): 2420–30. PMC 102731 . PMID 10871376. doi:10.1093/nar/28.12.2420. 
  • Wu L, Davies SL, Levitt NC, Hickson ID. Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51. J. Biol. Chem. 2001, 276 (22): 19375–81. PMID 11278509. doi:10.1074/jbc.M009471200. 
  • Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K, Kunkel TA, Groden J. The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair. J. Biol. Chem. 2001, 276 (32): 30031–5. PMID 11325959. doi:10.1074/jbc.M009664200. 
  • Wang XW, Tseng A, Ellis NA, Spillare EA, Linke SP, Robles AI, Seker H, Yang Q, Hu P, Beresten S, Bemmels NA, Garfield S, Harris CC. Functional interaction of p53 and BLM DNA helicase in apoptosis. J. Biol. Chem. 2001, 276 (35): 32948–55. PMID 11399766. doi:10.1074/jbc.M103298200. 
  • Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. Hum. Mol. Genet. 2001, 10 (12): 1287–98. PMID 11406610. doi:10.1093/hmg/10.12.1287. 
  • Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP. Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIα. Nucleic Acids Res. 2001, 29 (15): 3172–80. PMC 55826 . PMID 11470874. doi:10.1093/nar/29.15.3172. 

外部連結 编辑

  • GeneReviews/NCBI/NIH/UW entry on Bloom Syndrome (页面存档备份,存于互联网档案馆

布盧姆綜合症蛋白, bloom, syndrome, protein, 係一種由blm基因編碼的人類蛋白質, 在布盧姆綜合症患者體內不表達, 布盧姆綜合徵蛋白blm有效结构pdb, 直系同源检索, pdbe, rcsbpdb查询代码列表2kv2, 2mh9, 2rrd, 3we2, 3we3, 4cdg, 4cgz, 4o3m标识代号blm, recq2, recql2, recql3扩展标识遗传学, 604610, 鼠基因, 1328362, 同源基因, 47902, chembl, 1293237, genec. 布盧姆綜合症蛋白 Bloom syndrome protein 係一種由BLM基因編碼的人類蛋白質 在布盧姆綜合症患者體內不表達 1 布盧姆綜合徵蛋白BLM有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表2KV2 2MH9 2RRD 3WE2 3WE3 4CDG 4CGZ 4O3M标识代号BLM BS RECQ2 RECQL2 RECQL3扩展标识遗传学 604610 鼠基因 1328362 同源基因 47902 ChEMBL 1293237 GeneCards BLM GeneEC編號3 6 4 12基因本体论描述分子功能 bubble DNA binding p53 binding single stranded DNA binding ATP dependent DNA helicase activity helicase activity protein binding ATP binding ATP dependent helicase activity four way junction helicase activity ATPase activity annealing helicase activity ATP dependent 3 5 DNA helicase activity G quadruplex DNA binding细胞成分 nuclear chromosome chromosome telomeric region lateral element male germ cell nucleus nucleus nucleoplasm replication fork nucleolus cytoplasm nuclear matrix PML body pronucleus生物过程 regulation of cyclin dependent protein serine threonine kinase activity telomere maintenance double strand break repair via homologous recombination DNA double strand break processing DNA strand renaturation DNA repair DNA recombination cellular response to DNA damage stimulus mitotic G2 DNA damage checkpoint response to X ray protein sumoylation replication fork processing DNA duplex unwinding post translational protein modification cellular protein metabolic process positive regulation of transcription DNA templated negative regulation of DNA recombination negative regulation of mitotic recombination alpha beta T cell differentiation positive regulation of alpha beta T cell proliferation replication fork protection regulation of binding protein oligomerization negative regulation of cell division negative regulation of thymocyte apoptotic process cellular response to ionizing radiation cellular response to hydroxyurea cellular response to camptothecinSources Amigo QuickGO直系同源体物种人类小鼠Entrez64112144EnsemblENSG00000197299ENSMUSG00000030528UniProtP54132O88700mRNA序列NM 000057NM 001042527蛋白序列NP 000048NP 001035992基因位置Chr 15 90 72 90 82 MbChr 7 80 45 80 54 MbPubMed查询 1 2 查论编布盧姆綜合症基因編碼的產物和RecQ 英语 RecQ 家族的DExH盒包含DNA解旋酶有關聯 同時有DNA刺激ATP酶和ATP依賴性DNA解旋酶活性 布盧姆綜合症患者的DNA突變導致布盧姆綜合症蛋白的解旋酶模體損壞或發生改變 可能使得酶失去3 5 解旋酶活性 正常的布盧姆綜合症蛋白還可能參與對不恰當的同源重組的抑制 2 目录 1 減數分裂 2 交互作用 3 參考 4 拓展閱讀 5 外部連結減數分裂 编辑 nbsp 一個正常的減數分裂模型 以一個雙鏈DNA分子斷裂開始 緊隨與同源染色體的配對 以及介導重組修復過程的鏈插入過程 對DNA分子的斷裂的修復可以使得交叉互換發生 crossover 縮寫爲C0 也可能使得交叉互換不發生 non crossover 縮寫爲NCO 一個名爲 雙霍利迪交叉 Double Holliday Junction DHJ 的模型可以概述發生交叉互換的重組 CO 的情況 如右上方所示 不發生交叉互換的重組 NCO 基本可由合成依賴鏈退火 Synthesis Dependent Strand Annealing SDSA 模型來解釋 如左上方所示 大部分的重組都符合SDSA模型減數分裂的重組通常始於DNA雙鏈的斷裂 DNA double strand break DSB 在重組中 DNA斷裂區的5 端鏈的前段部分會通過一個名爲切除 resection 的過程被切去 在鏈插入的過程中 自由的3 端DNA會插入同源染色體未斷裂的相應區域 在鏈插入後 會通過不同的途徑發生交叉互換發生 crossover 縮寫爲C0 或交叉互換不發生 non crossover 縮寫爲NCO 的重組 具體可參見條目基因重組 芽殖酵母釀酒酵母 S cerevisiae 編碼一種與布盧姆綜合症蛋白同源的蛋白 名爲Sgs1 英语 Sgs1 小生長抑制物1 Small growth suppressor 1 Sgs1係一種在同源重組過程中的DNA修復中發揮作用的解旋酶 Sgs1解旋酶可能是釀酒酵母減數分裂過程中的大部分重組事件的調控物質 3 在正常的減數分裂過程中 Sgs1負責介導交叉互換不發生或發生霍利迪交叉的分子的重組 後一種情況的分子發生的是交叉互換發生的重組 3 在植物擬南芥 A thaliana 體內 布盧姆綜合症蛋白的同源解旋酶是減數分裂中交叉互換發生的重組進行的主要抑制物 4 這類解旋酶替換了插入鏈 使得它能與其它的黏性3 端發生退火 通過上述的SDSA過程使得交叉互換不發生的重組發生 根據估計 只有4 的DNA雙鏈斷裂 DSB 以交叉互換發生的重組爲結果 5 Sequela Arnaud等人 4 認爲交叉互換發生的重組受限是因爲交叉互換發生的重組 CO 長期成本 交叉互換發生的重組會打亂自然選擇選出的有利的基因 交互作用 编辑布盧姆綜合症蛋白可與以下蛋白質發生交互作用 運動失調性毛細血管擴張症突變蛋白 英语 Ataxia telangiectasia mutated ATM 6 7 CHAF1A 英语 CHAF1A 8 CHEK1 英语 CHEK1 9 FANCM 英语 FANCM 10 FEN1 英语 Flap structure specific endonuclease 1 11 H2AFX 英语 H2AFX 9 MLH1 英语 MLH1 6 12 13 14 P53 9 15 16 17 RAD51L3 英语 RAD51L3 18 RAD51 19 RPA1 英语 Replication protein A1 20 21 22 TOP3A 英语 TOP3A 12 20 23 24 TP53BP1 英语 TP53BP1 9 WRN 英语 Werner syndrome ATP dependent helicase 25 XRCC2 英语 XRCC2 18 參考 编辑 Karow JK Chakraverty RK Hickson ID The Bloom s syndrome gene product is a 3 5 DNA helicase J Biol Chem January 1998 272 49 30611 4 PMID 9388193 doi 10 1074 jbc 272 49 30611 Bloom syndrome Genetics Home Reference NIH 19 March 2013 原始内容存档于2016 07 27 3 0 3 1 De Muyt A Jessop L Kolar E Sourirajan A Chen J Dayani Y Lichten M BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism Mol Cell 2012 46 1 43 53 PMC 3328772 nbsp PMID 22500736 doi 10 1016 j molcel 2012 02 020 4 0 4 1 Seguela Arnaud M Crismani W Larcheveque C Mazel J Froger N Choinard S Lemhemdi A Macaisne N Van Leene J Gevaert K De Jaeger G Chelysheva L Mercier R Multiple mechanisms limit meiotic crossovers TOP3a and two BLM homologs antagonize crossovers in parallel to FANCM Proc Natl Acad Sci U S A 2015 112 15 4713 8 PMC 4403193 nbsp PMID 25825745 doi 10 1073 pnas 1423107112 Crismani W Girard C Froger N Pradillo M Santos JL Chelysheva L et al FANCM limits meiotic crossovers Science 2012 336 6088 1588 90 PMID 22723424 doi 10 1126 science 1220381 已忽略未知参数 author name separator 帮助 已忽略未知参数 author separator 帮助 6 0 6 1 Wang Y Cortez D Yazdi P Neff N Elledge SJ Qin J BASC a super complex of BRCA1 associated proteins involved in the recognition and repair of aberrant DNA structures Genes Dev April 2000 14 8 927 39 PMC 316544 nbsp PMID 10783165 doi 10 1101 gad 14 8 927 Beamish H Kedar P Kaneko H Chen P Fukao T Peng C Beresten S Gueven N Purdie D Lees Miller S Ellis N Kondo N Lavin MF Functional link between BLM defective in Bloom s syndrome and the ataxia telangiectasia mutated protein ATM J Biol Chem August 2002 277 34 30515 23 PMID 12034743 doi 10 1074 jbc M203801200 Jiao R Bachrati CZ Pedrazzi G Kuster P Petkovic M Li JL Egli D Hickson ID Stagljar I Physical and functional interaction between the Bloom s syndrome gene product and the largest subunit of chromatin assembly factor 1 Mol Cell Biol June 2004 24 11 4710 9 PMC 416397 nbsp PMID 15143166 doi 10 1128 MCB 24 11 4710 4719 2004 9 0 9 1 9 2 9 3 Sengupta S Robles AI Linke SP Sinogeeva NI Zhang R Pedeux R Ward IM Celeste A Nussenzweig A Chen J Halazonetis TD Harris CC Functional interaction between BLM helicase and 53BP1 in a Chk1 mediated pathway during S phase arrest J Cell Biol September 2004 166 6 801 13 PMC 2172115 nbsp PMID 15364958 doi 10 1083 jcb 200405128 Deans AJ West SC FANCM connects the genome instability disorders Bloom s Syndrome and Fanconi Anemia Mol Cell 24 December 2009 36 6 943 53 PMID 20064461 doi 10 1016 j molcel 2009 12 006 Sharma S Sommers JA Wu L Bohr VA Hickson ID Brosh RM Stimulation of flap endonuclease 1 by the Bloom s syndrome protein J Biol Chem March 2004 279 11 9847 56 PMID 14688284 doi 10 1074 jbc M309898200 12 0 12 1 Freire R d Adda Di Fagagna F Wu L Pedrazzi G Stagljar I Hickson ID Jackson SP Cleavage of the Bloom s syndrome gene product during apoptosis by caspase 3 results in an impaired interaction with topoisomerase IIIalpha Nucleic Acids Res August 2001 29 15 3172 80 PMC 55826 nbsp PMID 11470874 doi 10 1093 nar 29 15 3172 Langland G Kordich J Creaney J Goss KH Lillard Wetherell K Bebenek K Kunkel TA Groden J The Bloom s syndrome protein BLM interacts with MLH1 but is not required for DNA mismatch repair J Biol Chem August 2001 276 32 30031 5 PMID 11325959 doi 10 1074 jbc M009664200 Pedrazzi G Perrera C Blaser H Kuster P Marra G Davies SL Ryu GH Freire R Hickson ID Jiricny J Stagljar I Direct association of Bloom s syndrome gene product with the human mismatch repair protein MLH1 Nucleic Acids Res November 2001 29 21 4378 86 PMC 60193 nbsp PMID 11691925 doi 10 1093 nar 29 21 4378 Wang XW Tseng A Ellis NA Spillare EA Linke SP Robles AI Seker H Yang Q Hu P Beresten S Bemmels NA Garfield S Harris CC Functional interaction of p53 and BLM DNA helicase in apoptosis J Biol Chem August 2001 276 35 32948 55 PMID 11399766 doi 10 1074 jbc M103298200 Garkavtsev IV Kley N Grigorian IA Gudkov AV The Bloom syndrome protein interacts and cooperates with p53 in regulation of transcription and cell growth control Oncogene December 2001 20 57 8276 80 PMID 11781842 doi 10 1038 sj onc 1205120 Yang Q Zhang R Wang XW Spillare EA Linke SP Subramanian D Griffith JD Li JL Hickson ID Shen JC Loeb LA Mazur SJ Appella E Brosh RM Karmakar P Bohr VA Harris CC The processing of Holliday junctions by BLM and WRN helicases is regulated by p53 J Biol Chem August 2002 277 35 31980 7 PMID 12080066 doi 10 1074 jbc M204111200 18 0 18 1 Braybrooke JP Li JL Wu L Caple F Benson FE Hickson ID Functional interaction between the Bloom s syndrome helicase and the RAD51 paralog RAD51L3 RAD51D J Biol Chem November 2003 278 48 48357 66 PMID 12975363 doi 10 1074 jbc M308838200 Wu L Davies SL Levitt NC Hickson ID Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51 J Biol Chem June 2001 276 22 19375 81 PMID 11278509 doi 10 1074 jbc M009471200 20 0 20 1 Brosh RM Li JL Kenny MK Karow JK Cooper MP Kureekattil RP Hickson ID Bohr VA Replication protein A physically interacts with the Bloom s syndrome protein and stimulates its helicase activity J Biol Chem August 2000 275 31 23500 8 PMID 10825162 doi 10 1074 jbc M001557200 Opresko PL von Kobbe C Laine JP Harrigan J Hickson ID Bohr VA Telomere binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases J Biol Chem October 2002 277 43 41110 9 PMID 12181313 doi 10 1074 jbc M205396200 Moens PB Kolas NK Tarsounas M Marcon E Cohen PE Spyropoulos B The time course and chromosomal localization of recombination related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA DNA interactions without reciprocal recombination J Cell Sci April 2002 115 Pt 8 1611 22 PMID 11950880 Wu L Davies SL North PS Goulaouic H Riou JF Turley H Gatter KC Hickson ID The Bloom s syndrome gene product interacts with topoisomerase III J Biol Chem March 2000 275 13 9636 44 PMID 10734115 doi 10 1074 jbc 275 13 9636 Hu P Beresten SF van Brabant AJ Ye TZ Pandolfi PP Johnson FB Guarente L Ellis NA Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability Hum Mol Genet June 2001 10 12 1287 98 PMID 11406610 doi 10 1093 hmg 10 12 1287 von Kobbe C Karmakar P Dawut L Opresko P Zeng X Brosh RM Hickson ID Bohr VA Colocalization physical and functional interaction between Werner and Bloom syndrome proteins J Biol Chem June 2002 277 24 22035 44 PMID 11919194 doi 10 1074 jbc M200914200 拓展閱讀 编辑Woo LL Onel K Ellis NA The broken genome genetic and pharmacologic approaches to breaking DNA Ann Med 2007 39 3 208 18 PMID 17457718 doi 10 1080 08035250601167136 McDaniel LD Schultz RA Elevated sister chromatid exchange phenotype of Bloom syndrome cells is complemented by human chromosome 15 Proc Natl Acad Sci U S A 1992 89 17 7968 72 PMC 49836 nbsp PMID 1518822 doi 10 1073 pnas 89 17 7968 Ellis NA Groden J Ye TZ Straughen J Lennon DJ Ciocci S Proytcheva M German J The Bloom s syndrome gene product is homologous to RecQ helicases Cell 1995 83 4 655 66 PMID 7585968 doi 10 1016 0092 8674 95 90105 1 German J Roe AM Leppert MF Ellis NA Bloom syndrome an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26 1 Proc Natl Acad Sci U S A 1994 91 14 6669 73 PMC 44264 nbsp PMID 8022833 doi 10 1073 pnas 91 14 6669 Foucault F Vaury C Barakat A Thibout D Planchon P Jaulin C Praz F Amor Gueret M Characterization of a new BLM mutation associated with a topoisomerase II alpha defect in a patient with Bloom s syndrome Hum Mol Genet 1998 6 9 1427 34 PMID 9285778 doi 10 1093 hmg 6 9 1427 Kaneko H Orii KO Matsui E Shimozawa N Fukao T Matsumoto T Shimamoto A Furuichi Y Hayakawa S Kasahara K Kondo N BLM the causative gene of Bloom syndrome protein translocation into the nucleus by a nuclear localization signal Biochem Biophys Res Commun 1997 240 2 348 53 PMID 9388480 doi 10 1006 bbrc 1997 7648 Wu L Davies SL North PS Goulaouic H Riou JF Turley H Gatter KC Hickson ID The Bloom s syndrome gene product interacts with topoisomerase III J Biol Chem 2000 275 13 9636 44 PMID 10734115 doi 10 1074 jbc 275 13 9636 Yankiwski V Marciniak RA Guarente L Neff NF Nuclear structure in normal and Bloom syndrome cells Proc Natl Acad Sci U S A 2000 97 10 5214 9 PMC 25808 nbsp PMID 10779560 doi 10 1073 pnas 090525897 Wang Y Cortez D Yazdi P Neff N Elledge SJ Qin J BASC a super complex of BRCA1 associated proteins involved in the recognition and repair of aberrant DNA structures Genes Dev 2000 14 8 927 39 PMC 316544 nbsp PMID 10783165 doi 10 1101 gad 14 8 927 Karow JK Constantinou A Li JL West SC Hickson ID The Bloom s syndrome gene product promotes branch migration of Holliday junctions Proc Natl Acad Sci U S A 2000 97 12 6504 8 PMC 18638 nbsp PMID 10823897 doi 10 1073 pnas 100448097 Brosh RM Li JL Kenny MK Karow JK Cooper MP Kureekattil RP Hickson ID Bohr VA Replication protein A physically interacts with the Bloom s syndrome protein and stimulates its helicase activity J Biol Chem 2000 275 31 23500 8 PMID 10825162 doi 10 1074 jbc M001557200 Dutertre S Ababou M Onclercq R Delic J Chatton B Jaulin C Amor Gueret M Cell cycle regulation of the endogenous wild type Bloom s syndrome DNA helicase Oncogene 2000 19 23 2731 8 PMID 10851073 doi 10 1038 sj onc 1203595 Barakat A Ababou M Onclercq R Dutertre S Chadli E Hda N Benslimane A Amor Gueret M Identification of a novel BLM missense mutation 2706T gt C in a Moroccan patient with Bloom s syndrome Hum Mutat 2000 15 6 584 5 PMID 10862105 doi 10 1002 1098 1004 200006 15 6 lt 584 AID HUMU28 gt 3 0 CO 2 I Brosh RM Karow JK White EJ Shaw ND Hickson ID Bohr VA Potent inhibition of Werner and Bloom helicases by DNA minor groove binding drugs Nucleic Acids Res 2000 28 12 2420 30 PMC 102731 nbsp PMID 10871376 doi 10 1093 nar 28 12 2420 Wu L Davies SL Levitt NC Hickson ID Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51 J Biol Chem 2001 276 22 19375 81 PMID 11278509 doi 10 1074 jbc M009471200 Langland G Kordich J Creaney J Goss KH Lillard Wetherell K Bebenek K Kunkel TA Groden J The Bloom s syndrome protein BLM interacts with MLH1 but is not required for DNA mismatch repair J Biol Chem 2001 276 32 30031 5 PMID 11325959 doi 10 1074 jbc M009664200 Wang XW Tseng A Ellis NA Spillare EA Linke SP Robles AI Seker H Yang Q Hu P Beresten S Bemmels NA Garfield S Harris CC Functional interaction of p53 and BLM DNA helicase in apoptosis J Biol Chem 2001 276 35 32948 55 PMID 11399766 doi 10 1074 jbc M103298200 Hu P Beresten SF van Brabant AJ Ye TZ Pandolfi PP Johnson FB Guarente L Ellis NA Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability Hum Mol Genet 2001 10 12 1287 98 PMID 11406610 doi 10 1093 hmg 10 12 1287 Freire R d Adda Di Fagagna F Wu L Pedrazzi G Stagljar I Hickson ID Jackson SP Cleavage of the Bloom s syndrome gene product during apoptosis by caspase 3 results in an impaired interaction with topoisomerase IIIa Nucleic Acids Res 2001 29 15 3172 80 PMC 55826 nbsp PMID 11470874 doi 10 1093 nar 29 15 3172 外部連結 编辑GeneReviews NCBI NIH UW entry on Bloom Syndrome 页面存档备份 存于互联网档案馆 取自 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