PPL2 Translesion Polymerase Is Essential for the Completion of Chromosomal DNA Replication in the African Trypanosome
In: Molecular Cell, Jg. 52 (2013-11-01), Heft 4, S. 554-565
Online
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Zugriff:
Summary 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.
Graphical Abstract
Highlights • Trypanosomatids contain two archaeo-eukaryotic primase-polymerase-like proteins • PPL2 is essential in the pathogenic bloodstream form African trypanosome • PPL2 suppresses DNA damage and allows completion of chromosomal replication • PPL2 mediates translesion DNA synthesis
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PPL2 Translesion Polymerase Is Essential for the Completion of Chromosomal DNA Replication in the African Trypanosome
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Autor/in / Beteiligte Person: | Rudd, Sean G. ; Horn, David ; Glover, Lucy ; Doherty, Aidan J. ; Jozwiakowski, Stanislaw K. ; University of Sussex ; London School of Hygiene and Tropical Medicine (LSHTM) ; This research was supported by grants from Biotechnology and Biological Sciences Research Council (A.J.D.), a centre grant from the MRC (A.J.D.), and by The Wellcome Trust (grants 089172/Z/09/Z and 093010/Z/10/Z to D.H.). D.H. is a Wellcome Trust Senior Investigator (100320/Z/12/Z). S.G.R. was supported by a MRC DTA PhD studentship. |
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Zeitschrift: | Molecular Cell, Jg. 52 (2013-11-01), Heft 4, S. 554-565 |
Veröffentlichung: | Elsevier BV, 2013 |
Medientyp: | unknown |
ISSN: | 1097-2765 (print) |
DOI: | 10.1016/j.molcel.2013.10.034 |
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