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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 G 2 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 invitro, 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.
|Number of pages||12|
|Early online date||21 Nov 2013|
|Publication status||Published - 21 Nov 2013|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
FingerprintDive into the research topics of 'PPL2 translesion polymerase is essential for the completion of chromosomal DNA replication in the african trypanosome'. Together they form a unique fingerprint.
- 1 Finished
High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
1/09/13 → 29/02/20