在Y系聚合酶中的乌比基结合域调节转化合成
Marzena Bienko1, Catherine M Green, Nicola Crosetto
1Institute for Biochemistry II, Goethe University Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Science (New York, N.Y.)
|December 17, 2005
概括
研究人员在Y-家族聚合酶中发现了在DNA损伤中转化合成 (TLS) 所必不可少的泛素结合域. 这些域促进聚合酶招募和DNA修复,这对于细胞对DNA损伤的反应至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 转载合成 (TLS) 是哺乳动物细胞中关键的DNA修复途径,可以在DNA损伤中进行复制.
- 众所周知,增殖细胞核抗原 (PCNA) 的ubiquitination可以在DNA损伤时将复制机制直接导向TLS途径.
- 细胞在TLS中识别和解释PCNA无处不在的精确机制仍然不完全理解.
研究的目的:
- 在转化合成过程中识别和表征涉及无化PCNA识别的新型蛋白质域.
- 阐明这些域在Y家族DNA聚合酶的招募和活性中的功能意义.
主要方法:
- 在Y家族TLS聚合酶中识别保存的泛素结合域 (UBM和UBZ).
- 生物化学试验,以评估聚合酶与乌比奎和单乌比奎PCNA的结合.
- 细胞局部化研究,观察复制工厂中的聚合酶积累.
- 功能补充测定在色素变体 (XP-V) 纤维细胞中.
主要成果:
- 在Y-家族TLS聚合酶中发现了两个进化保守的泛素结合域,UBM和UBZ.
- 这些域调节聚合酶eta (poleta) 和iota (poliota) 与ubiquitin的结合.
- 已识别的域对于这些聚合酶在复制工厂的积累及其与单基化PCNA的相互作用至关重要.
- 波尔塔的UBZ域对于恢复XP-V细胞正常的紫外线 (UV) 辐射反应至关重要.
结论:
- 在Y家族聚合酶中的乌比基结合域 (UBM和UBZ) 是转化合成途径的关键调节者.
- 这些域促进TLS聚合酶通过与单基化PCNA相互作用而被招募到DNA病变中.
- 这些发现为控制DNA损伤耐受性和修复的分子机制提供了关键的见解.
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