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This Week in Cell: Jul 14, 2010

In Cell this week, an international research team reports their identification of KIAA1018/MTMR15/FAN1, a highly conserved protein, which is "recruited to sites of DNA damage by the monoubiquitinated form of FANCD2." FAN1 depletion in human cells, the team shows, results in a hypersensitivity to interstrand crosslinks, ICL repair-related issues, and genome instability. "These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair," the authors say.

In this week's Cell Stem Cell, investigators at the Mount Sinai Hospital Center for Systems Biology in Toronto and their colleagues demonstrate with functional genomics that somatic cell reprogramming involves a multi-step mechanism encompassing a BMP-miRNA-MET — mesenchymal-to-epithelial transition — axis. Using a secondary MEF model, which "forms iPSCs with high efficiency upon inducible expression of Oct4, Klf4, c-Myc, and Sox2," the authors examined gene expression data and RNAi screens to determine the steps involved in the reprogramming process.

Another paper in Cell Stem Cell this week outlines a "distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal." Specifically, researchers at the University of Toronto and their international colleagues report that human HSCs show "delayed DNA double-strand break rejoining, persistent γH2AX foci, and enhanced p53- and ASPP1-dependent apoptosis after γ-radiation compared to progenitors." HSCs with inactivated p53 show reduced self-renewal, the authors write; the team suggests that their study reveals unique roles for p53 — the regulation of apoptosis and the prevention of γH2AX foci accumulation — that "ensure optimal HSC function" upon self-renewal.

Scientists in Canada report their identification of the opposite roles of Msi2 and Prox1 in the regulation of HSC activity using an RNAi functional genetics approach. Prox1 knockdown, the authors write, "led to in vivo accumulation of primitive and differentiated cells." Their subsequent gene-expression profiling experiments "identified a number of known HSC and cell cycle regulators as potential downstream targets to Msi2 and Prox1," the team says.

The Scan

Genetic Risk Factors for Hypertension Can Help Identify Those at Risk for Cardiovascular Disease

Genetically predicted high blood pressure risk is also associated with increased cardiovascular disease risk, a new JAMA Cardiology study says.

Circulating Tumor DNA Linked to Post-Treatment Relapse in Breast Cancer

Post-treatment detection of circulating tumor DNA may identify breast cancer patients who are more likely to relapse, a new JCO Precision Oncology study finds.

Genetics Influence Level of Depression Tied to Trauma Exposure, Study Finds

Researchers examine the interplay of trauma, genetics, and major depressive disorder in JAMA Psychiatry.

UCLA Team Reports Cost-Effective Liquid Biopsy Approach for Cancer Detection

The researchers report in Nature Communications that their liquid biopsy approach has high specificity in detecting all- and early-stage cancers.