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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

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posted on 2023-06-08, 16:12 authored by Sean G Rudd, Lucy Glover, Stanislaw K Jozwiakowski, David Horn, Aidan DohertyAidan Doherty
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular Cell

ISSN

1097-2765

Publisher

Elsevier

Issue

4

Volume

52

Page range

554-565

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2013-10-28

First Open Access (FOA) Date

2014-07-01

First Compliant Deposit (FCD) Date

2013-11-29

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