DNA polymerase lambda (Pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis

DNA polymerase lambda (Pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis
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DOI:
10.1006/jmbi.2000.4005
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发表时间:
2000-08-25
影响因子:
5.6
通讯作者:
Blanco, L
Blanco, L
中科院分区:
生物学2区
文献类型:
--
作者:
García-Díaz, M;Domínguez, O;Blanco, L

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在小鼠19号染色体上发现了一种编码新型DNA聚合酶(Pol lambda)的新基因(POLL)。鼠Pol λ由573个氨基酸残基组成,与Poi β具有32%的同一性,参与真核细胞中的核DNA修复。有趣的是,Pol lambda包含参与DNA结合、核苷酸结合和选择以及DNA聚合催化的所有关键残基,其在Poi beta和属于X家族的其他DNA聚合酶中是保守的。鼠Poi λ,在大肠杆菌中过度生产,显示内在的DNA聚合酶活性时,通过原位凝胶分析评估。Poi λ还保留了Poi β的关键残基,这些残基是其固有的脱氧核糖磷酸裂解酶(dRhD)活性所需的。Poi lambda的前230个氨基酸残基在Pol beta中没有对应物,含有BRCT结构域,存在于多种细胞周期检查点控制蛋白中,这些蛋白对DNA损伤和参与DNA修复的蛋白质有反应。北方印迹、原位杂交和免疫组化结果表明,Poi lambda在睾丸中特异性表达,受发育调控,主要与粗线期精母细胞相关。这些第一个证据,虽然是间接的,但表明Pol lambda在与减数分裂相关的DNA修复合成中的潜在作用。(C)北京大学出版社.
A new gene (POLL) encoding a novel DNA polymerase (Pol lambda) has been identified at mouse chromosome 19. Murine Pol lambda, consisting of 573 amino acid residues, has a 32% identity to Poi beta, involved in nuclear DNA repair in eukaryotic cells. It is interesting that Pol lambda contains all the critical residues involved in DNA binding, nucleotide binding and selection, and catalysis of DNA polymerization, that are conserved in Poi beta and other DNA polymerases belonging to family X. Murine Poi lambda, overproduced in Escherichia coli, displayed intrinsic DNA polymerase activity when assessed by in situ gel analysis. Poi lambda also conserves the critical residues of Poi beta required for its intrinsic deoxyribose phosphate lyase (dRPase) activity. The first 230 amino acid residues of Poi lambda, that have no counterpart in Pol beta, contain a BRCT domain, present in a variety of cell-cycle check-point control proteins responsive to DNA damage and proteins involved in DNA repair. Northern blotting, in situ hybridization analysis and immunostaining showed high levels of Poi lambda specifically expressed in testis, being developmentally regulated and mainly associated to pachytene spermatocytes. These first evidences, although indirect, suggest a potential role of Pol lambda in DNA repair synthesis associated with meiosis. (C) 2000 Academic Press.