Kannouche Patricia L, Lehmann Alan R
Laboratory of Genetic Instability and Cancer, CNRS, Institut Gustave Roussy, Villejuif, France.
Cell Cycle. 2004 Aug;3(8):1011-3. Epub 2004 Aug 7.
Replicative DNA polymerases are blocked by damage in the template DNA. To get past this damage, the cell employs specialized translesion synthesis (TLS) polymerases, which have reduced stringency and are able to bypass different lesions. For example, DNA polymerase eta (poleta) is able to carry out TLS past UV-induced cyclobutane pyrimidine dimers. How does the cell bring about the switch from replicative to TLS polymerase? We have shown that, in human cells, when the replication machinery is blocked at DNA damage, PCNA, the sliding clamp required for DNA replication, is mono-ubiquitinated and that this modified form of PCNA has increased affinity for poleta. This provides a mechanism for the polymerase switch. In this Extra-View, we discuss the possible signals that might trigger ubiquitination of PCNA, whether PCNA becomes de-ubiquitinated after TLS has been accomplished and the role of the hREV1 protein in TLS. We point out some apparent differences between mechanisms in Saccharomyces cerevisiae and human cells.
复制性DNA聚合酶会被模板DNA中的损伤所阻断。为了克服这种损伤，细胞会利用专门的跨损伤合成（TLS）聚合酶，这些聚合酶的严格性较低，能够绕过不同的损伤。例如，DNA聚合酶η（polη）能够在紫外线诱导的环丁烷嘧啶二聚体处进行跨损伤合成。细胞是如何实现从复制性聚合酶向TLS聚合酶的转换的呢？我们已经表明，在人类细胞中，当复制机制在DNA损伤处受阻时，DNA复制所需的滑动夹PCNA会发生单泛素化，并且这种修饰形式的PCNA对polη的亲和力增加。这为聚合酶转换提供了一种机制。在这篇扩展观点文章中，我们讨论了可能触发PCNA泛素化的信号、TLS完成后PCNA是否会去泛素化以及hREV1蛋白在TLS中的作用。我们指出了酿酒酵母和人类细胞机制之间的一些明显差异。
