In a paper published online in advance in Science this week, investigators at Harvard Medical School and their colleagues show that the "phosphorylation of histone H3 threonine-3 (H3T3ph) by Haspin is necessary for chromosomal passenger complex accumulation at centromeres, and that the CPC subunit Survivin binds directly to H3T3ph." They also show that a non-binding Survivin-D70A/D71A mutant "does not support centromeric CPC concentration, and both Haspin depletion and Survivin-D70A/D71A mutation diminish centromere localization of MCAK and mitotic checkpoint signaling in taxol." The authors suggest that H3T3ph is critical for positioning the CPC at the centromeres during mitosis.
In a Perspectives piece published in this week's Science, Darren Hutt and William Balch at the Scripps Research Institute discuss "the proteome in balance," and reference a recent paper by Okiyoneda et al., which shows that the proteostasis network "operates globally, constantly surveying protein folds, from co-translational insertion of proteins into the endoplasmic reticulum to removal of unstable proteins at the plasma membrane." Hutt and Balch say that "although various chemical, biochemical, and physiological approaches could solve the folding and trafficking defects in one cellular locale," based on the work of Okiyoneda and colleagues, "we must ultimately address the folding and function problem for the cell as a whole through the malleable proteostasis network."
Over at Science Signaling, researchers at Zhejiang University in China report that "FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair." The team explains that Fanconi anemia-associated nuclease 1 is a previously unrecognized nuclease which they've characterized in their investigations. FAN1, they write, "promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex," and thus, it facilitates the repair of DNA interstrand cross-links.
In an editorial in Science Translational Medicine this week, Eric Topol of the Scripps Translational Research Institute contemplates the combination of pharmacy benefit managers, pharmacies, and pharmacogenetic testing, and asks whether it is a "prescription for progress." Topol reports that "while clinicians have been reluctant to routinely use pharmacogenomic analyses to guide their prescribing practices, pharmacy benefit managers and drugstores are proceeding with major pharmacogenetic initiatives," and discusses the implications of this. Our sister publication Pharmacogenomics Reporter has a Q&A with Topol here.