The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation.
The human gastric cancer-associated DNA polymerase β variant D160N is a mutator that induces cellular transformation.
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人胃癌相关的DNA聚合酶β变异D160N是一种诱导细胞转化的突变器。
DOI：
10.1016/j.dnarep.2012.01.004
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发表时间：
2012-04-01
期刊：
影响因子：
3.8
通讯作者：
Sweasy, Joann B.
中科院分区：
文献类型：
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作者：
Donigan, Katherine A.;Hile, Suzanne E.;Eckert, Kristin A.;Sweasy, Joann B.
到目前为止，大约30%的人类肿瘤测序在POLB基因中含有突变，而这些突变在匹配的正常组织中不存在。许多突变产生含有非同义单氨基酸取代的酶，其中几种已被发现具有异常活性或保真度，并在表达时转化细胞。DNA聚合酶β（Pol β）变体Asp160Asn（D160N）首次在胃肿瘤中被鉴定。D160 N在细胞中的表达诱导细胞转化，如通过过度增殖、病灶形成、锚定非依赖性生长和侵袭所测量的。在这里，我们表明，D160 N是一个活跃的增变聚合酶，诱导复杂的突变。我们的数据支持这样的解释，即复杂的诱变是所观察到的细胞表型的潜在机制，所有这些表型都与肿瘤发生或肿瘤进展有关。
Approximately 30% of human tumors sequenced to date harbor mutations in the POLB gene that are not present in matched normal tissue. Many mutations give rise to enzymes that contain non-synonymous single amino acid substitutions, several of which have been found to have aberrant activity or fidelity and transform cells when expressed. The DNA Polymerase β (Pol β) variant Asp160Asn (D160N) was first identified in a gastric tumor. Expression of D160N in cells induces cellular transformation as measured by hyperproliferation, focus formation, anchorage-independent growth and invasion. Here, we show that D160N is an active mutator polymerase that induces complex mutations. Our data support the interpretation that complex mutagenesis is the underlying mechanism of the observed cellular phenotypes, all of which are linked to tumorigenesis or tumor progression.
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影响因子：
2.9
作者：
Dalal, S;Hile, S;Sweasy, JB
通讯作者：
Sweasy, JB
影响因子：
4.8
作者：
Srivastava, DK;Vande Berg, BJ;Wilson, SH
通讯作者：
Wilson, SH
影响因子：
2.8
作者：
Bielas, JH;Loeb, LA
通讯作者：
Loeb, LA
影响因子：
4.8
作者：
Fortini, P;Parlanti, E;Dogliotti, E
通讯作者：
Dogliotti, E
DOI：
10.1073/pnas.78.5.2727
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LAW, MF;LOWY, DR;HOWLEY, PM
通讯作者：
HOWLEY, PM