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<jats:title>Cancer epigenetics in the driver's seat</jats:title> <jats:p> Recent cancer genome projects unexpectedly highlighted the role of epigenetic alterations in cancer development. About half of human cancers were found to harbor mutations in chromatin proteins. In a Review, Flavahan <jats:italic>et al.</jats:italic> propose that chromatin and epigenetic aberrations have the potential to confer on cells the full range of oncogenic properties represented in the classic “hallmarks” depiction of cancer. They suggest that genetic, environmental, and metabolic factors can make chromatin aberrantly permissive or restrictive. Permissive chromatin creates a state of “epigenetic plasticity,” which can activate oncogene expression or cell fate changes that drive cancer development. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6348" page="eaal2380" related-article-type="in-this-issue" vol="357" xlink:href="10.1126/science.aal2380">eaal2380</jats:related-article> </jats:p>

<jats:p> O’Brien <jats:italic>et al</jats:italic> . (Research Article, 24 February 2017, eaag1789) proposed a novel mechanism of primase function based on redox activity of the iron-sulfur cluster buried inside the C-terminal domain of the large primase subunit (p58C). Serious problems in the experimental design and data interpretation raise concerns about the validity of the conclusions. </jats:p>

<jats:p> O’Brien <jats:italic>et al</jats:italic> . (Research Article, 24 February 2017, eaag1789) report that the iron-sulfur cluster of primase has a redox role in enzyme activity. Their analysis is based on a partially misfolded structure of the iron-sulfur cluster domain of primase. In the correctly folded structure, two of the three tyrosines putatively involved in electron transfer, Y345 and Y347, contact the RNA/DNA helix, providing an alternative explanation for the data of O’Brien <jats:italic>et al</jats:italic> . </jats:p>

<jats:p> Baranovskiy <jats:italic>et al</jats:italic> . and Pellegrini argue that, based on structural data, the path for charge transfer through the [4Fe4S] domain of primase is not feasible. Our manuscript presents electrochemical data directly showing charge transport through DNA to the [4Fe4S] cluster of a primase p58C construct and a reversible switch in the DNA-bound signal with oxidation/reduction, which is inhibited by mutation of three tyrosine residues. Although the dispositions of tyrosines differ in different constructs, all are within range for microsecond electron transfer. </jats:p>