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- W74846869 abstract "Genome stability is of upmost importance to life. DNA polymerases are essential for theduplication and maintenance of the genome but they cannot themselves begin synthesisof a DNA chain, and require the activity of specialised RNA polymerases called primases.In eukaryotic cells distinct enzymes catalyse these two essential processes. This thesiscontains the characterisation of coiled-coil domain containing protein (CCDC)111, apreviously uncharacterised protein conserved in a broad range of unicellular andmulticellular eukaryotes including humans. CCDC111 is a member of the archaeaoeukaroyticprimase (AEP) superfamily and uniquely for a eukaryotic enzyme possessesboth primase and polymerase activities, and was thus renamed PrimPol. The work in thisthesis implicates PrimPol in the process of DNA damage tolerance, a universalmechanism by which cells complete genome duplication in spite of potentially lethal DNAdamage. The first results chapters detail the essential role of a PrimPol homologue(TbPrimPol2) in the important protozoan pathogen Trypanosoma brucei. A combinationof molecular, cell biology, and biochemical analyses indicate a role for TbPrimPol2 in thepost-replication tolerance of endogenously occurring DNA damage using its trans-lesionDNA synthesis activity. The remaining results chapters characterise PrimPol in humancultured cells, and demonstrate that this enzyme is present in both the nucleus andmitochondria. In the nucleus PrimPol functions in the cellular tolerance of ultraviolet (UV)-induced DNA damage, and is required to protect xeroderma pigmentosum variant (XP-V)cells, deficient in the UV lesion bypass polymerase Pol !, from the cytotoxic affects ofUV radiation. Together, this thesis establishes the involvement of PrimPol in DNAdamage tolerance from one of the earliest diverging eukaryotic organisms to man." @default.
- W74846869 created "2016-06-24" @default.
- W74846869 creator A5042397070 @default.
- W74846869 date "2013-07-30" @default.
- W74846869 modified "2023-09-26" @default.
- W74846869 title "Cellular and biochemical characterisation of PrimPol, a novel eukaryotic primase-polymerase involved in DNA damage tolerance" @default.
- W74846869 hasPublicationYear "2013" @default.
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