Research ArticleCell Biology

A Nontranscriptional Role for HIF-1α as a Direct Inhibitor of DNA Replication

See allHide authors and affiliations

Science Signaling  12 Feb 2013:
Vol. 6, Issue 262, pp. ra10
DOI: 10.1126/scisignal.2003417

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

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.

View Full Text