Enzymatic release of 5'-terminal deoxyribose phosphate residues from damaged DNA in human cells.

Enzymatic release of 5'-terminal deoxyribose phosphate residues from damaged DNA in human cells.
复制标题

从人类细胞中受损的 DNA 中酶促释放 5-末端脱氧核糖磷酸残基。

DOI:
10.1021/bi00099a020
复制
发表时间:
1991
期刊:
影响因子:
2.9
通讯作者:
T. Lindahl
T. Lindahl
中科院分区:
生物学3区
文献类型:
--
作者:
A. Price;T. Lindahl

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在几种人细胞系和小牛胸腺的可溶性提取物中,已经鉴定出催化或促进5 '-末端脱氧核糖磷酸残基从先前被AP内切核酸酶切割的DNA脱碱基位点释放的活性。从脱嘌呤/脱嘧啶位点切除无碱基糖磷酸残基预期在通过缺口填充和连接修复之前是必须的。最有效的切除功能是由于DNA脱氧核糖磷酸二酯酶类似于大肠杆菌中发现的蛋白质。人酶已部分纯化,并从可检测的核酸外切酶活性中释放出来。这种DNA脱氧核糖磷酸二酯酶是一种需要Mg(2+)的水解酶,表观分子量约为47 kDa,位于细胞核中。相比之下,主要的核5 '----3'核酸外切酶,DNA酶IV,不能催化5 '-末端脱氧核糖磷酸残基作为游离糖磷酸的释放,但可以以缓慢的速率释放它们作为小寡核苷酸的一部分。与酶促水解相比,通过多胺和碱性蛋白促进的β-消除从DNA中非酶促去除5 '-末端脱氧核糖磷酸是非常缓慢的释放机制。我们的结论是,DNA脱氧核糖磷酸二酯酶的行为之间的中间阶段的AP核酸内切酶和DNA聚合酶在哺乳动物细胞中的脱嘌呤/apyrimidinc网站的DNA修复过程中,但也存在几种替代途径的脱氧核糖磷酸残基的切除。
Activities that catalyze or promote the release of 5'-terminal deoxyribose phosphate residues from DNA abasic sites previously incised by an AP endonuclease have been identified in soluble extracts of several human cell lines and calf thymus. Such excision of base-free sugar phosphate residues from apurinic/apyrimidinic sites is expected to be obligatory prior to repair by gap filling and ligation. The most efficient excision function is due to a DNA deoxyribophosphodiesterase similar to the protein found in Escherichia coli. The human enzyme has been partially purified and freed from detectable exonuclease activity. This DNA deoxyribophosphodiesterase is a Mg(2+)-requiring hydrolytic enzyme with an apparent molecular mass of approximately 47 kDa and is located in the cell nucleus. By comparison, the major nuclear 5'----3' exonuclease, DNase IV, is unable to catalyze the release of 5'-terminal deoxyribose phosphate residues as free sugar phosphates but can liberate them at a slow rate as part of small oligonucleotides. Nonenzymatic removal of 5'-terminal deoxyribose phosphate from DNA by beta-elimination promoted by polyamines and basic proteins is a very slow mechanism of release compared to enzymatic hydrolysis. We conclude that a DNA deoxyribophosphodiesterase acts at an intermediate stage between an AP endonuclease and a DNA polymerase during DNA repair at apurinic/apyrimidinc sites in mammalian cells, but several alternative routes also exist for the excision of deoxyribose phosphate residues.
包含 SV40 复制起点的 DNA 的完整酶促合成。
DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
作者:
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大肠杆菌 DNA 聚合酶 I 在修复内切脱氧核糖核酸酶产生的切口处的作用特征。
DOI: --
发表时间: 1982
期刊: The Journal of biological chemistry
影响因子: --
作者:
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通讯作者: Linn,S
DOI: --
发表时间: 1988-07
期刊: The Journal of biological chemistry
影响因子: --
作者:
M. Kenny;L. A. Balogh;J. Hurwitz
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DOI: 10.1021/bi00218a033
发表时间: 1991-01-29
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
MAZUMDER, A;GERLT, JA;BOLTON, PH
通讯作者: BOLTON, PH