布盧姆綜合症蛋白

布盧姆綜合徵蛋白; BLM
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB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 Gene
EC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 camptothecin;
	Sources: Amigo / QuickGO
直系同源体

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]。

布盧姆綜合症基因編碼的產物和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

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（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

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（ATM）[6][7]
CHAF1A[8]
CHEK1[9]
FANCM[10]
FEN1[11]
H2AFX[9]
MLH1[6][12][13][14]
P53[9][15][16][17]
RAD51L3[18]
RAD51[19]
RPA1[20][21][22]
TOP3A[12][20][23][24]
TP53BP1[9]
WRN[25]
XRCC2[18]

參考

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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. . J. Biol. Chem. August 2002, 277 (35): 31980–7. PMID 12080066. doi:10.1074/jbc.M204111200.
Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID. . J. Biol. Chem. November 2003, 278 (48): 48357–66. PMID 12975363. doi:10.1074/jbc.M308838200.
Wu L, Davies SL, Levitt NC, Hickson ID. . J. Biol. Chem. June 2001, 276 (22): 19375–81. PMID 11278509. doi:10.1074/jbc.M009471200.
Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA. . 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. . 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. . 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. . J. Biol. Chem. March 2000, 275 (13): 9636–44. PMID 10734115. doi:10.1074/jbc.275.13.9636.
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von Kobbe C, Karmakar P, Dawut L, Opresko P, Zeng X, Brosh RM, Hickson ID, Bohr VA. . J. Biol. Chem. June 2002, 277 (24): 22035–44. PMID 11919194. doi:10.1074/jbc.M200914200.

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Wu L, Davies SL, Levitt NC, Hickson ID. . 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. . 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. . 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. . 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. . Nucleic Acids Res. 2001, 29 (15): 3172–80. PMC 55826 . PMID 11470874. doi:10.1093/nar/29.15.3172.

外部連結

GeneReviews/NCBI/NIH/UW entry on Bloom Syndrome （页面存档备份，存于）

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[pmid9388193-1] Karow JK, Chakraverty RK, Hickson ID. . J Biol Chem. January 1998, 272 (49): 30611–4. PMID 9388193. doi:10.1074/jbc.272.49.30611.

[2] . Genetics Home Reference. NIH. [19 March 2013]. （原始内容存档于2016-07-27）.

[De-3] De Muyt A, Jessop L, Kolar E, Sourirajan A, Chen J, Dayani Y, Lichten M. . Mol. Cell. 2012, 46 (1): 43–53. PMC 3328772 . PMID 22500736. doi:10.1016/j.molcel.2012.02.020.

[Mazel-4] 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. . Proc. Natl. Acad. Sci. U.S.A. 2015, 112 (15): 4713–8. PMC 4403193 . PMID 25825745. doi:10.1073/pnas.1423107112.

[pmid22723424-5] Crismani, W; Girard, C; Froger, N; Pradillo, M; Santos, JL; Chelysheva, L; et al. . 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)

[pmid10783165-6] Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J. . Genes Dev. April 2000, 14 (8): 927–39. PMC 316544 . PMID 10783165. doi:10.1101/gad.14.8.927.

[pmid12034743-7] 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. . J. Biol. Chem. August 2002, 277 (34): 30515–23. PMID 12034743. doi:10.1074/jbc.M203801200.

[pmid15143166-8] Jiao R, Bachrati CZ, Pedrazzi G, Kuster P, Petkovic M, Li JL, Egli D, Hickson ID, Stagljar I. . Mol. Cell. Biol. June 2004, 24 (11): 4710–9. PMC 416397 . PMID 15143166. doi:10.1128/MCB.24.11.4710-4719.2004.

[pmid15364958-9] Sengupta S, Robles AI, Linke SP, Sinogeeva NI, Zhang R, Pedeux R, Ward IM, Celeste A, Nussenzweig A, Chen J, Halazonetis TD, Harris CC. . J. Cell Biol. September 2004, 166 (6): 801–13. PMC 2172115 . PMID 15364958. doi:10.1083/jcb.200405128.

[10] Deans AJ, West SC. . Mol. Cell. 24 December 2009, 36 (6): 943–53. PMID 20064461. doi:10.1016/j.molcel.2009.12.006.

[pmid14688284-11] Sharma S, Sommers JA, Wu L, Bohr VA, Hickson ID, Brosh RM. . J. Biol. Chem. March 2004, 279 (11): 9847–56. PMID 14688284. doi:10.1074/jbc.M309898200.

[pmid11470874-12] Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP. . Nucleic Acids Res. August 2001, 29 (15): 3172–80. PMC 55826 . PMID 11470874. doi:10.1093/nar/29.15.3172.

[pmid11325959-13] Langland G, Kordich J, Creaney J, Goss KH, Lillard-Wetherell K, Bebenek K, Kunkel TA, Groden J. . J. Biol. Chem. August 2001, 276 (32): 30031–5. PMID 11325959. doi:10.1074/jbc.M009664200.

[pmid11691925-14] Pedrazzi G, Perrera C, Blaser H, Kuster P, Marra G, Davies SL, Ryu GH, Freire R, Hickson ID, Jiricny J, Stagljar I. . Nucleic Acids Res. November 2001, 29 (21): 4378–86. PMC 60193 . PMID 11691925. doi:10.1093/nar/29.21.4378.

[pmid11399766-15] 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. . J. Biol. Chem. August 2001, 276 (35): 32948–55. PMID 11399766. doi:10.1074/jbc.M103298200.

[pmid11781842-16] Garkavtsev IV, Kley N, Grigorian IA, Gudkov AV. . Oncogene. December 2001, 20 (57): 8276–80. PMID 11781842. doi:10.1038/sj.onc.1205120.

[pmid12080066-17] 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. . J. Biol. Chem. August 2002, 277 (35): 31980–7. PMID 12080066. doi:10.1074/jbc.M204111200.

[pmid12975363-18] Braybrooke JP, Li JL, Wu L, Caple F, Benson FE, Hickson ID. . J. Biol. Chem. November 2003, 278 (48): 48357–66. PMID 12975363. doi:10.1074/jbc.M308838200.

[pmid11278509-19] Wu L, Davies SL, Levitt NC, Hickson ID. . J. Biol. Chem. June 2001, 276 (22): 19375–81. PMID 11278509. doi:10.1074/jbc.M009471200.

[pmid10825162-20] Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA. . J. Biol. Chem. August 2000, 275 (31): 23500–8. PMID 10825162. doi:10.1074/jbc.M001557200.

[pmid12181313-21] Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID, Bohr VA. . J. Biol. Chem. October 2002, 277 (43): 41110–9. PMID 12181313. doi:10.1074/jbc.M205396200.

[pmid11950880-22] Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B. . J. Cell. Sci. April 2002, 115 (Pt 8): 1611–22. PMID 11950880.

[pmid10734115-23] Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID. . J. Biol. Chem. March 2000, 275 (13): 9636–44. PMID 10734115. doi:10.1074/jbc.275.13.9636.

[pmid11406610-24] Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA. . Hum. Mol. Genet. June 2001, 10 (12): 1287–98. PMID 11406610. doi:10.1093/hmg/10.12.1287.

[pmid11919194-25] von Kobbe C, Karmakar P, Dawut L, Opresko P, Zeng X, Brosh RM, Hickson ID, Bohr VA. . J. Biol. Chem. June 2002, 277 (24): 22035–44. PMID 11919194. doi:10.1074/jbc.M200914200.