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- Title
Pol η is required for DNA replication during nucleotide deprivation by hydroxyurea.
- Authors
de Feraudy, S.; Limoli, C. L.; Giedzinski, E.; Karentz, D.; Marti, T. M.; Feeney, L.; Cleaver, J. E.
- Abstract
Hydroxyurea reduces DNA replication by nucleotide deprivation, whereas UV damage generates DNA photoproducts that directly block replication fork progression. We show that the low fidelity class Y polymerase Pol η is recruited to proliferating cell nuclear antigen at replication forks both by hydroxyurea and UV light. Under nucleotide deprivation, Pol η allows cells to accumulate at the G1/S boundary by facilitating slow S-phase progression and promotes apoptosis. Normal cells consequently enter apoptosis at a faster rate than Pol η-deficient cells. Coincident with hydroxyurea-induced S-phase delay, Pol η-deficient cells undergo more replication fork breakage and accumulate more foci of the Mre11/Rad50/Nbs1 complex and phosphorylated histone H2AX. We conclude that under conditions of nucleotide deprivation, Pol η is required for S-phase progression but is proapoptotic. However, as Pol η is reported to require higher nucleotide concentrations than class B replicative polymerases, its recruitment by hydroxyurea requires it to function under suboptimal conditions. Our results suggest that hydroxyurea-induced apoptosis occurs at the G1/S boundary and that initiation of the S-phase requires greater nucleotide concentrations than does S-phase progression.Oncogene (2007) 26, 5713–5721. doi:10.1038/sj.onc.1210385; published online 19 March 2007
- Subjects
DNA replication; NUCLEOTIDES; ULTRAVIOLET radiation; APOPTOSIS; DNA synthesis; ANTIGENS
- Publication
Oncogene, 2007, Vol 26, Issue 39, p5713
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1210385