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专门的DNA聚合酶,细胞存活,以及突变的起源

Errol C Friedberg¹, Robert Wagner, Miroslav Radman

¹Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. errol.friedberg@utsouthwestern.edu

Science (New York, N.Y.)

|June 1, 2002

概括

专门的DNA聚合酶绕过DNA损伤,防止细胞死亡. 虽然它们在受损DNA上是准确的,但在未受损DNA上它们的低保真度可能有助于产生免疫多样性等功能.

科学领域:

分子生物学分子生物学
遗传学是一个遗传学.
生物化学生物化学

背景情况:

细胞死亡可能是由于DNA受损或改变时复制停止而发生的.
多个DNA聚合酶存在于细胞中,专门绕过DNA损伤.
转载DNA合成 (TLS) 聚合酶对于复制受损DNA至关重要.

研究的目的:

在转化DNA合成过程中调查专门的DNA聚合酶的忠实性.
了解DNA聚合酶忠实性对受损和未受损DNA的影响.
探索低保真度DNA合成的潜在生理作用.

主要方法:

对DNA聚合酶活性和忠实性的分析.
在体外检测转化DNA合成的试验.
对DNA聚合酶基质特异性的检查.

主要成果:

专门的DNA聚合酶有效地绕过特定的DNA病变,具有高保真度.
这些聚合酶在未受损的DNA上表现出显著降低的忠诚度.
在未受损的DNA上观察到低保真度,即使在非同源性病变中也是如此.

结论:

专门的DNA聚合酶对于防止DNA损伤导致细胞死亡至关重要.
一些聚合酶在未受损的DNA上的降低忠实度是关键特征.
这种低保真度可能是一个功能机制,例如,在产生免疫球蛋白多样性.

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