PMID- 30471195 OWN - NLM STAT- MEDLINE DCOM- 20200706 LR - 20200706 IS - 1462-5822 (Electronic) IS - 1462-5814 (Linking) VI - 21 IP - 4 DP - 2019 Apr TI - Chlamydia trachomatis impairs host base excision repair by downregulating polymerase beta. PG - e12986 LID - 10.1111/cmi.12986 [doi] AB - 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 beta was downregulated in infected cells associated with upregulation of microRNA-499a (miR-499a). Stabilising polymerase beta 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 beta by direct inhibition through miR-499a and downregulation of p53 debilitate the host-cell base excision repair during C. trachomatis infection. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Gulve, Nitish AU - Gulve N AD - Department of Microbiology, University of Wuerzburg Biocenter, Wuerzburg, Germany. FAU - Prusty, Bhupesh K AU - Prusty BK AD - Department of Microbiology, University of Wuerzburg Biocenter, Wuerzburg, Germany. FAU - Rudel, Thomas AU - Rudel T AUID- ORCID: 0000-0003-4740-6991 AD - Department of Microbiology, University of Wuerzburg Biocenter, Wuerzburg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190109 PL - India TA - Cell Microbiol JT - Cellular microbiology JID - 100883691 SB - IM MH - Chlamydia Infections/*metabolism/parasitology MH - Chlamydia trachomatis/*pathogenicity MH - DNA Damage/genetics/physiology MH - DNA Repair/genetics/physiology MH - Down-Regulation MH - Epithelial Cells/*metabolism/*parasitology MH - Female MH - Humans MH - Immunoblotting MH - Ovary/cytology MH - Real-Time Polymerase Chain Reaction EDAT- 2018/11/25 06:00 MHDA- 2020/07/07 06:00 CRDT- 2018/11/25 06:00 PHST- 2018/04/25 00:00 [received] PHST- 2018/10/22 00:00 [revised] PHST- 2018/11/22 00:00 [accepted] PHST- 2018/11/25 06:00 [pubmed] PHST- 2020/07/07 06:00 [medline] PHST- 2018/11/25 06:00 [entrez] AID - 10.1111/cmi.12986 [doi] PST - ppublish SO - Cell Microbiol. 2019 Apr;21(4):e12986. doi: 10.1111/cmi.12986. Epub 2019 Jan 9.