Interaction of human DNA polymerase η with monoubiquitinated PCNA:: A possible mechanism for the polymerase switch in response to DNA damage
Interaction of human DNA polymerase η with monoubiquitinated PCNA:: A possible mechanism for the polymerase switch in response to DNA damage
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DOI：
10.1016/s1097-2765(04)00259-x
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发表时间：
2004-05-21
期刊：
影响因子：
16
通讯作者：
Lehmann, AR
中科院分区：
文献类型：
--
作者：
Kannouche, PL;Wing, J;Lehmann, AR
大多数类型的DNA损伤在DNA合成期间阻断复制叉进展，因为复制型DNA聚合酶不能在其活性位点容纳改变的DNA碱基。为了克服这个障碍，真核细胞采用专门的跨损伤合成（TLS）聚合酶，它可以插入核苷酸对受损的碱基。特别地，通过DNA聚合酶eta（poleta）的TLS是绕过UV光产物的主要途径。细胞如何在阻断的分叉位点从复制型转换为TLS聚合酶尚不清楚。我们表明，在人类细胞中，PCNA成为monoubiquitinated后，紫外线照射的细胞，这是依赖于hRad18蛋白。Monoubiquitinated PCNA，而不是未修饰的PCNA特异性地与poleta相互作用，我们已经确定了两个图案在poleta参与这种相互作用。我们的研究结果提供了一个有吸引力的机制，通过该机制，PCNA的monoubiquitination可能介导聚合酶开关。
Most types of DNA damage block replication fork progression during DNA synthesis because replicative DNA polymerases are unable to accommodate altered DNA bases in their active sites. To overcome this block, eukaryotic cells employ specialized translesion synthesis (TLS) polymerases, which can insert nucleotides opposite damaged bases. In particular, TLS by DNA polymerase eta (poleta) is the major pathway for bypassing UV photoproducts. How the cell switches from replicative to TLS polymerase at the site of blocked forks is unknown. We show that, in human cells, PCNA becomes monoubiquitinated following UV irradiation of the cells and that this is dependent on the hRad18 protein. Monoubiquitinated PCNA but not unmodified PCNA specifically interacts with poll, and we have identified two motifs in poleta that are involved in this interaction. Our findings provide an attractive mechanism by which monoubiquitination of PCNA might mediate the polymerase switch.