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Protective role of Puralpha to cisplatin
Rafal Kaminski1, Armine Darbinyan, Nana Merabova
1Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Background:
The nucleic acid-binding protein Puralpha is involved at stalled DNA replication forks, in double-strand break (DSB) DNA repair and the cellular response to DNA replication stress. Puralpha also regulates homologous recombination-directed DNA repair (HRR).
Results:
Cells lacking Puralpha showed enhanced sensitivity to cisplatin as evaluated by assays for cell viability and cell clonogenicity. This was seen both in Puralpha-negative MEFs and in human glioblastoma cells treated with siRNA directed against Puralpha. MEFs lacking Puralpha also showed enhanced H2AX phosphorylation in response to cisplatin. Repair of a reporter plasmid that had been treated with cisplatin was decreased in a reactivation assay using Puralpha-negative MEFs and the capacity of nuclear extracts from Puralpha-negative MEFs to perform non-homologous end-joining in vitro was also impaired.
Methods:
We investigated the effects of the DNA damage-inducing cancer chemotherapeutic agent cisplatin on mouse embryo fibroblasts (MEFs) from PURA(-/-) knockout mice that lack Puralpha.
Conclusions:
Puralpha has a role in the cellular response to cisplatin-induced DNA damage and may provide new therapeutic modalities for cisplatin-resistant tumors.
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