BIOGRID CURATED DATA FOR PUBLICATION: Noncanonical role of the 9-1-1 clamp in the error-free DNA damage tolerance pathway.

Protein-Protein, Genetic, and Chemical Interactions for Karras GI (2013):Noncanonical role of the 9-1-1 clamp in the error-free DNA damage tolerance pathway. curated by BioGRID (https://thebiogrid.org); ABSTRACT: Damaged DNA is an obstacle during DNA replication and a cause of genome instability and cancer. To bypass this problem, eukaryotes activate DNA damage tolerance (DDT) pathways that involve ubiquitylation of the DNA polymerase clamp proliferating cell nuclear antigen (PCNA). Monoubiquitylation of PCNA mediates an error-prone pathway by recruiting translesion polymerases, whereas polyubiquitylation activates an error-free pathway that utilizes undamaged sister chromatids as templates. The error-free pathway involves recombination-related mechanisms; however, the factors that act along with polyubiquitylated PCNA remain largely unknown. Here we report that the PCNA-related 9-1-1 complex, which is typically linked to checkpoint signaling, participates together with Exo1 nuclease in error-free DDT. Notably, 9-1-1 promotes template switching in a manner that is distinct from its canonical checkpoint functions and uncoupled from the replication fork. Our findings thus reveal unexpected cooperation in the error-free pathway between the two related clamps and indicate that 9-1-1 plays a broader role in the DNA damage response than previously assumed.

蛋白质-蛋白质、遗传学及化学相互作用数据集，源自Karras GI (2013)的研究：《9-1-1夹子的非典型作用在无错误DNA损伤耐受途径中的角色》。本数据集由BioGRID（https://thebiogrid.org）整理；摘要：DNA损伤在DNA复制过程中构成障碍，并引发基因组不稳定性及癌症。为了规避这一问题，真核生物激活了涉及DNA聚合酶夹蛋白PCNA泛素化的DNA损伤耐受（DDT）途径。PCNA的单泛素化通过募集跨损伤聚合酶介导一种易错途径，而多泛素化则激活一种无错误途径，该途径利用未损伤的姐妹染色单体作为模板。无错误途径涉及重组相关机制；然而，与多泛素化PCNA共同作用的因子尚鲜为人知。在本研究中，我们报道了PCNA相关的9-1-1复合物，通常与检查点信号传导相关联，与Exo1核酸酶协同参与无错误DDT。值得注意的是，9-1-1通过一种不同于其典型检查点功能的方式促进模板转换，并且与复制叉解耦。我们的研究结果揭示了两个相关夹子在无错误途径中的意外合作，并表明9-1-1在DNA损伤反应中的作用比先前假设的更为广泛。