X-ray structure of the complex of regulatory subunits of human DNA polymerase delta.

X-ray structure of the complex of regulatory subunits of human DNA polymerase delta.
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DOI:
10.4161/cc.7.19.6720
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发表时间:
2008-10
期刊:
Cell cycle (Georgetown, Tex.)
影响因子:
--
通讯作者:
Tahirov TH
Tahirov TH
中科院分区:
其他
文献类型:
--
作者:
Baranovskiy AG;Babayeva ND;Liston VG;Rogozin IB;Koonin EV;Pavlov YI;Vassylyev DG;Tahirov TH

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真核生物DNA聚合酶δ(POLδ)参与基因组复制、同源重组、DNA修复和损伤耐受。POLδ功能的调节依赖于第二(P50)和第三(P66)非催化亚基之间的相互作用。我们报道了p50·p66N复合体的晶体结构,在p50中具有寡核苷酸结合和磷酸二酯酶结构域,在p66中具有带翼的螺旋-转弯-螺旋N-末端结构域。通过战略性氨基酸变化破坏p50和p66酵母同源物之间的相互作用,导致对冷敏感性、对羟基脲的敏感性和减少紫外线诱变,模拟缺乏POLδ第三亚单位的菌株的表型。除Polδ外,古生物和真核生物中所有B家族复制型DNA聚合酶的第二亚单位都具有类似于p50·p66N的三个结构域结构,这增加了编码p66的基因的一部分来自进化较晚的第二亚单位基因的可能性。
The eukaryotic DNA polymerase δ (Pol δ) participates in genome replication, homologous recombination, DNA repair and damage tolerance. Regulation of the plethora of Pol δ functions depends on the interaction between the second (p50) and third (p66) non-catalytic subunits. We report the crystal structure of p50•p66N complex featuring oligonucleotide binding and phosphodiesterase domains in p50 and winged helix-turn-helix N-terminal domain in p66. Disruption of the interaction between the yeast orthologs of p50 and p66 by strategic amino acid changes leads to cold-sensitivity, sensitivity to hydroxyurea and to reduced UV mutagenesis, mimicking the phenotypes of strains where the third subunit of Pol δ is absent. The second subunits of all B family replicative DNA polymerases in archaea and eukaryotes, except Pol δ, share a three-domain structure similar to p50•p66N, raising the possibility that a portion of the gene encoding p66 was derived from the second subunit gene relatively late in evolution.
DOI: 10.1016/s0092-8674(01)00367-1
发表时间: 2001-06-01
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影响因子: 64.5
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发表时间: 1998-09-01
期刊: ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子: --
作者:
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通讯作者: Warren, GL