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

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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

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布盧姆綜合症蛋白可與以下蛋白質發生交互作用

參考

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