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布卢姆综合症蛋白

维基百科,自由的百科全书
布卢姆综合征蛋白
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编号 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]

布卢姆综合症蛋白(Bloom syndrome protein),系一种由BLM基因编码的人类蛋白质,在布卢姆综合症患者体内不表达[1]

布卢姆综合症基因编码的产物和RecQ英语RecQ家族的DExH盒包含DNA解旋酶有关联,同时有DNA刺激ATP酶和ATP依赖性DNA解旋酶活性。布卢姆综合症患者的DNA突变导致布卢姆综合症蛋白的解旋酶模体损坏或发生改变,可能使得酶失去3'→5'解旋酶活性。正常的布卢姆综合症蛋白还可能参与对不恰当的同源重组的抑制[2]

减数分裂

一个正常的减数分裂模型,以一个双链DNA分子断裂开始,紧随与同源染色体的配对,以及介导重组修复过程的链插入过程。对DNA分子的断裂的修复可以使得交叉互换发生(crossover,缩写为C0),也可能使得交叉互换不发生(non-crossover,缩写为NCO)。一个名为“双霍利迪交叉”(Double Holliday Junction (DHJ))的模型可以概述发生交叉互换的重组(CO)的情况,如右上方所示。不发生交叉互换的重组(NCO)基本可由合成依赖链退火(Synthesis Dependent Strand Annealing (SDSA))模型来解释,如左上方所示。大部分的重组都符合SDSA模型

减数分裂重组通常始于DNA双链的断裂(DNA double-strand break (DSB))。在重组中,DNA断裂区的5'端链的前段部分会通过一个名为切除(resection)的过程被切去。在链插入的过程中,自由的3'端DNA会插入同源染色体未断裂的相应区域。在链插入后,会通过不同的途径发生交叉互换发生(crossover,缩写为C0)或交叉互换不发生(non-crossover,缩写为NCO)的重组(具体可参见条目基因重组)。

芽殖酵母酿酒酵母S.cerevisiae)编码一种与布卢姆综合症蛋白同源的蛋白,名为Sgs1英语Sgs1(小生长抑制物1,Small growth suppressor 1)。Sgs1系一种在同源重组过程中的DNA修复中发挥作用的解旋酶。Sgs1解旋酶可能是酿酒酵母减数分裂过程中的大部分重组事件的调控物质[3]。在正常的减数分裂过程中,Sgs1负责介导交叉互换不发生或发生霍利迪交叉的分子的重组,后一种情况的分子发生的是交叉互换发生的重组[3]

在植物拟南芥A.thaliana)体内,布卢姆综合症蛋白的同源解旋酶是减数分裂中交叉互换发生的重组进行的主要抑制物[4]。这类解旋酶替换了插入链,使得它能与其它的黏性3'端发生退火,通过上述的SDSA过程使得交叉互换不发生的重组发生。根据估计,只有4%的DNA双链断裂(DSB)以交叉互换发生的重组为结果[5]。Sequela-Arnaud等人[4]认为交叉互换发生的重组受限是因为交叉互换发生的重组(CO)长期成本——交叉互换发生的重组会打乱自然选择选出的有利的基因。

交互作用

布卢姆综合症蛋白可与以下蛋白质发生交互作用

参考

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