Rudd_Moll_Cell_PPL2_Translesion_2013.pdf (2.46 MB)
PPL2 translesion polymerase is essential for the completion of chromosomal DNA replication in the African trypanosome
journal contribution
posted on 2023-06-08, 16:12 authored by Sean G Rudd, Lucy Glover, Stanislaw K Jozwiakowski, David Horn, Aidan DohertyAidan DohertyFaithful 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.
History
Publication status
- Published
File Version
- Published version
Journal
Molecular CellISSN
1097-2765Publisher
ElsevierExternal DOI
Issue
4Volume
52Page range
554-565Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2013-10-28First Open Access (FOA) Date
2014-07-01First Compliant Deposit (FCD) Date
2013-11-29Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC