CNRS, UPR, Conventionné par l'Université d'Aix-Marseille, France.
DNA Repair (Amst). 2010 Aug 5;9(8):922-8. doi: 10.1016/j.dnarep.2010.04.010.
Replicative DNA polymerases duplicate genomes in a very efficient and accurate mode. However their progression can be blocked by DNA lesions since they are unable to accommodate bulky damaged bases in their active site. In response to replication blockage, monoubiquitination of PCNA promotes the switch between replicative and specialized polymerases proficient to overcome the obstacle. In this study, we characterize novel connections between proteins involved in replication and TransLesion Synthesis (TLS). We demonstrate that PDIP38 (Poldelta interacting protein of 38kDa) directly interacts with the TLS polymerase Poleta. Interestingly, the region of Poleta interacting with PDIP38 is found to be located within the ubiquitin-binding zinc finger domain (UBZ) of Poleta. We show that the depletion of PDIP38 increases the number of cells with Poleta foci in the absence of DNA damage and diminishes cell survival after UV irradiation. In addition, PDIP38 is able to interact directly not only with Poleta but also with the specialized polymerases Rev1 and Polzeta (via Rev7). We thus suggest that PDIP38 serves as a mediator protein helping TLS Pols to transiently replace replicative polymerases at damaged sites.
复制 DNA 聚合酶以非常高效和准确的模式复制基因组。然而，由于它们无法在其活性部位容纳体积较大的受损碱基，因此它们的进展可能会被 DNA 损伤所阻断。为了应对复制阻断，PCNA 的单泛素化促进了在有能力克服障碍的复制和专门聚合酶之间的转换。在这项研究中，我们描述了参与复制和跨损伤合成（TLS）的蛋白质之间的新联系。我们证明 PDIP38（Poldelta 相互作用蛋白 38kDa）与 TLS 聚合酶 Poleta 直接相互作用。有趣的是，与 PDIP38 相互作用的 Poleta 区域位于 Poleta 的泛素结合锌指结构域（UBZ）内。我们表明，PDIP38 的耗竭会增加没有 DNA 损伤时 Poleta 焦点的细胞数量，并减少 UV 照射后的细胞存活率。此外，PDIP38 不仅可以直接与 Poleta 相互作用，还可以与专门的聚合酶 Rev1 和 Polzeta（通过 Rev7）相互作用。因此，我们认为 PDIP38 是一种中介蛋白，有助于 TLS Pols 在受损部位瞬时替代复制聚合酶。
