PPL2 translesion polymerase is essential for the completion of chromosomal DNA replication in the African trypanosome

Rudd, Sean G, Glover, Lucy, Jozwiakowski, Stanislaw K, Horn, David and Doherty, Aidan J (2013) PPL2 translesion polymerase is essential for the completion of chromosomal DNA replication in the African trypanosome. Molecular Cell, 52 (4). pp. 554-565. ISSN 1097-2765

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Abstract

Faithful copying of the genome is essential for life. In
eukaryotes, a single archaeo-eukaryotic primase (AEP), DNA primase, is required for the initiation and progression of DNA replication. Here we have identified additional eukaryotic AEP-like proteins with DNA-dependent primase and/or polymerase activity. Uniquely, the genomes of trypanosomatids, a group of kinetoplastid protozoa of significant medical importance, encode two PrimPol-like (PPL) proteins. In the African trypanosome, PPL2 is a nuclear enzyme present in G2 phase cells. Following PPL2
knockdown, a cell-cycle arrest occurs after the bulk of DNA synthesis, the DNA damage response is activated, and cells fail to recover. Consistent with this phenotype, PPL2 replicates damaged DNA templates in vitro, including templates containing the UV-induced pyrimidine-pyrimidone (6-4) photoproduct. Furthermore, PPL2 accumulates at sites of nuclear DNA damage. Taken together, our results indicate an essential role for PPL2 in postreplication tolerance of endogenous DNA damage, thus allowing completion of genome duplication.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Related URLs:
Depositing User: Deeptima Massey
Date Deposited: 28 Oct 2013 15:31
Last Modified: 14 Mar 2017 14:02
URI: http://sro.sussex.ac.uk/id/eprint/46832

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