Catalytic and non-catalytic roles of DNA polymerase k in the protection of XXXX cells against genotoxic stresses.

@entity1 @entity6321 @entity137 @entity10842 @entity8197 @entity7097 @entity1138 @entity1050 @entity876 @entity273 @entity56 @entity164 @entity1732 @entity4624
DNA polymerase k (Pol k) is a specialized DNA polymerase involved in translesion DNA synthesis. Although its bypass activities across lesions are well characterized in biochemistry, its cellular protective roles against genotoxic insults are still elusive. To better understand the in vivo protective roles, we have established a @entity1 cell line deficient in the expression of Pol k (KO) and another expressing catalytically dead Pol k ( @entity1050 ), to examine the cytotoxic sensitivity to 11 genotoxins including ultraviolet C light (UV). These cell lines were established in a genetic background of @entity1 -MSH+, a @entity1 lymphoblastic cell line that has high efficiency for gene targeting, and functional @entity876 and mismatch repair activities. We classified the genotoxins into four groups. Group 1 includes @entity4624 , @entity1138 , and @entity1732 , where the sensitivity was equally higher in KO and @entity1050 than in the cell line expressing @entity164 ( @entity7097 ). Group 2 includes @entity273 and @entity8197 , where @entity56 was observed only in KO. Group 3 includes @entity10842 and @entity6321 , where @entity56 was observed only in @entity1050 . Group 4 includes UV and three chemicals, where the chemicals exhibited similar @entity137 to all three cell lines. The results suggest that Pol k not only protects cells from genotoxic DNA lesions via DNA polymerase activities, but also contributes to genome integrity by acting as a non-catalytic protein against oxidative damage caused by @entity273 and @entity8197 . The non-catalytic roles of Pol k in protection against oxidative damage by @entity273 are discussed.
