Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells.

Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells.
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在着色性干皮病变异细胞中传播的穿梭载体的紫外线超突变性。

DOI:
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发表时间:
1993
影响因子:
6.5
通讯作者:
Kenneth H. Kraemer
Kenneth H. Kraemer
中科院分区:
医学1区
文献类型:
--
作者:
H. Waters;S. Seetharam;Michael M. Seidman;Kenneth H. Kraemer

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变异型色素性干皮病(XP)患者的临床XP包括皮肤癌的频率很高,但与其他形式的XP相比,他们有正常的紫外线(UV)后DNA切除修复和几乎正常的紫外线后存活。然而,像切除修复缺陷的XP细胞一样,XP变异体细胞是紫外线高度可变的。我们使用紫外线处理的质粒穿梭载体pZ189来检测XP变异型患者XPPHBE和正常对照的淋巴母细胞DNA修复缺陷。质粒修复、突变和复制发生在转基因细胞内,这一过程取决于细胞的修复能力。对于紫外线照射后的XP变异细胞,质粒存活是正常的,但紫外线照射后有异常增加的质粒突变频率。对突变质粒的序列分析显示,XP变异细胞中具有单碱基替代突变的质粒的频率增加。在早期的紫外线诱变研究中,G:C->A:T碱基替换突变占主导地位,从两个细胞系中回收的质粒。从XP变异体细胞中回收的质粒组G:C-->C:G颠换频率显著高于正常细胞。标记基因突变的位置是非随机的,在从XP变异细胞和正常细胞中回收的质粒中发现了不同的诱变热点。这项研究提示,在紫外线存活正常的情况下,质粒紫外线的高度变异性可能与XP变异患者紫外线皮肤癌易感性增加有关。
Patients with the variant form of xeroderma pigmentosum (XP) have clinical XP including a high frequency of skin cancer but, in contrast to the other forms of XP, have normal post-ultraviolet (UV) DNA excision repair and nearly normal post-UV survival. However, like excision repair-deficient XP cells, the XP variant cells are UV hypermutable. We used a UV-treated plasmid shuttle vector, pZ189, to examine the DNA repair defect in lymphoblastoid cells from an XP variant patient, XPPHBE, and a normal control. Plasmid repair, mutagenesis, and replication occur within transfected cells in a process dependent on the cells' repair capacity. With the XP variant cells post-UV, plasmid survival was normal with but there was an abnormally increased post-UV plasmid mutation frequency. Sequence analysis of the mutated plasmids revealed an increased frequency of plasmids with single base substitution mutations with the XP variant cells. As in earlier studies with UV mutagenesis, there was a predominance of G:C-->A:T base substitution mutations with plasmids recovered from both cell lines. The frequency of G:C-->C:G transversions was significantly higher with plasmids recovered from the XP variant cells than from normal cells. The location of mutations in the marker gene was non-random with different mutagenic hotspots found in plasmids recovered from the XP variant cells and from the normal cells. This study suggests that plasmid UV hypermutability in the presence of normal UV survival may be related to the increased UV skin cancer susceptibility of XP variant patients.
DNA 聚合酶在非指导模板碱基取代诱变中的作用。
DOI: 10.1016/s0300-9084(82)80138-7
发表时间: 1982
期刊: Biochimie
影响因子: 3.9
作者:
Strauss,B;Rabkin,S;Sagher,D;Moore,P
通讯作者: Moore,P
DOI: 10.1021/bi00053a011
发表时间: 1993-01-19
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
JIANG, N;TAYLOR, JS
通讯作者: TAYLOR, JS
着色性干皮病变种,涉及多系统。
DOI: --
发表时间: 1992
影响因子: --
作者:
Hessel,A;Siegle,RJ;Mitchell,DL;Cleaver,JE
通讯作者: Cleaver,JE
DOI: 10.1073/pnas.88.17.7810
发表时间: 1991-09
影响因子: 11.1
作者:
Y. Wang;V. Maher;J. Mccormick
通讯作者: Y. Wang;V. Maher;J. Mccormick