Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools

dc.contributor.authorKoç, Ahmet
dc.contributor.authorWheeler, Linda J.
dc.contributor.authorMathews, Christopher K.
dc.date.accessioned2017-06-19T13:02:21Z
dc.date.available2017-06-19T13:02:21Z
dc.date.issued2003
dc.departmentİnönü Üniversitesien_US
dc.descriptionJ Biol Chemen_US
dc.description.abstractThe relationship between dNTP levels and DNA synthesis was investigated using factor-synchronized yeast treated with the ribonucleotide reductase inhibitor hydroxyurea (HU). Although HU blocked DNA synthesis and prevented the dNTP pool expansion that normally occurs at G1/S, it did not exhaust the levels of any of the four dNTPs, which dropped to about 80% of G1 levels. When dbf4 yeast that are ts for replication initiation were allowed to preaccumulate dNTPs at 37 °C before being released to 25 °C in the presence of HU, they synthesized 0.3 genome equivalents of DNA and then arrested as dNTPs approached sub-G1 levels. Accumulation of dNTPs at G1/S was not a prerequisite for replication initiation, since dbf4 cells incubated in HU at 25 °C were able to replicate when subsequently switched to 37 °C in the absence of HU. The replication arrest mechanism was not dependent on the Mec1/ Rad53 pathway, since checkpoint-deficient rad53 cells also failed to exhaust basal dNTPs when incubated in HU. The persistence of basal dNTP levels in HU-arrested cells and partial bypass of the arrest in cells that had preaccumulated dNTPs suggest that cells have a mechanism for arresting DNA chain elongation when dNTP levels are not maintained above a critical threshold.en_US
dc.identifier.citationKOÇ, A., Wheeler, L., Mathews, C., & Gary, M. (2003). Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools . J Biol Chem, (279(1)), 223–0.en_US
dc.identifier.endpage0en_US
dc.identifier.issue1en_US
dc.identifier.startpage223en_US
dc.identifier.urihttp://www.jbc.org/content/279/1/223.full.pdf
dc.identifier.urihttps://hdl.handle.net/11616/7112
dc.identifier.volume279en_US
dc.language.isoenen_US
dc.publisherJ Biol Chemen_US
dc.relation.ispartofJ Biol Chemen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleHydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP poolsen_US
dc.typeArticleen_US

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