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Sci. Signal., 12 February 2013
Vol. 6, Issue 262, p. ra10
Staying Wound Up During Hypoxia
Decreased oxygen availability (a condition called hypoxia) triggers various cellular responses, such as increased activity of hypoxia-inducible factor 1 (HIF-1), a transcription factor that activates genes involved in helping cells to survive oxygen deprivation. Hubbi et al. found that the HIF-1α subunit also had a nontranscriptional role in cellular responses to hypoxia. Hypoxic cells undergo cell cycle arrest, and HIF-1α altered interactions between the minichromosome maintenance (MCM) helicase, which unwinds DNA in preparation for replication, and various binding partners, leading to inhibition of MCM helicase activation and decreased DNA replication. HIF-1α mutants lacking transcriptional activity retained the ability to decrease DNA replication and to induce cell cycle arrest. HIF-1α can therefore mediate adaptive cellular responses to hypoxia through both transcriptional and nontranscriptional mechanisms.
Citation: M. E. Hubbi, Kshitiz, D. M. Gilkes, S. Rey, C. C. Wong, W. Luo, D.-H. Kim, C. V. Dang, A. Levchenko, G. L. Semenza, A Nontranscriptional Role for HIF-1α as a Direct Inhibitor of DNA Replication. Sci. Signal.6, ra10 (2013).