DNA polymerase λ, a novel DNA repair enzyme in human cells
DNA polymerase λ, a novel DNA repair enzyme in human cells
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DOI：
10.1074/jbc.m111601200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Blanco, L
中科院分区：
文献类型：
--
作者：
García-Díaz, M;Bebenek, K;Blanco, L
DNA 聚合酶 lambda (pol lambda) 是一种新型 X 家族 DNA 聚合酶，已被认为在减数分裂重组和 DNA 修复中发挥作用。最近证明 pol lambda 中固有的 5'-脱氧核糖-5-磷酸裂合酶活性支持该酶在碱基切除修复中的功能。然而，这种酶的聚合活性的生化特性仍然很大程度上未知。我们已经以可溶性活性形式克隆并纯化了均质的人 pol lambda，并且我们在此提出了其聚合特征的生化描述。为了支持 DNA 修复中的作用，pol lambda 以 DNA 模板依赖性方式插入核苷酸，并在含有 5'-磷酸基团的小间隙中持续进行。这些特性，连同其核苷酸插入保真度参数和缺乏校对活性，表明 pol lambda 是一种新型的 β 样 DNA 聚合酶。然而，polk lambda 对 dNTP 的高亲和力（是 pol beta 的 37 倍）与其可能参与 DNA、在低细胞水平的 dNTP 下发生的交易相一致。这表明，尽管 pol beta 和 pol lambda 有相似之处，但它们具有非冗余的体内功能。
DNA polymerase lambda (pol lambda) is a novel family X DNA polymerase that has been suggested to play a role In meiotic recombination and DNA repair. The recent demonstration of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in pol lambda supports a function of this enzyme in base excision repair. However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown. We have cloned and purified human pol lambda to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features. In support of a role in DNA repair, pol lambda inserts nucleotides in a DNA template-dependent manner and is processive in small gaps containing a 5'-phosphate group. These properties, together with its nucleotide insertion fidelity parameters and lack of proofreading activity, indicate that pol lambda is a novel beta-like DNA polymerase. However, the high affinity of polk lambda for dNTPs (37-fold over pol beta) is consistent with its possible involvement in DNA, transactions occurring under low cellular levels of dNTPs. This suggests that, despite their similarities, pol beta and pol lambda have nonredundant in vivo functions.