Chlamydia trachomatis impairs host base excision repair by downregulating polymerase β.

Abstract

Chlamydia trachomatis infections have been associated with ovarian cancer by several epidemiological studies. Here, we show that C.trachomatis-infected primary human ovarian epithelial cells display elevated oxidative DNA damage. Base excision repair, an important cellular mechanism to repair oxidative DNA lesions, was impaired in infected primary ovarian and in several other types of cells. Polymerase β was downregulated in infected cells associated with upregulation of microRNA-499a (miR-499a). Stabilising polymerase β by inhibiting miR-499a significantly improved repair. Moreover, downregulation of tumour suppressor p53 also resulted in attenuated repair in these cells. Thus, our data show that downregulation of polymerase β by direct inhibition through miR-499a and downregulation of p53 debilitate the host-cell base excision repair during C.trachomatis infection.