Mechanism of tandem duplication formation in BRCA1-mutant cells.

Small, approximately 10-kilobase microhomology-mediated tandem duplications are abundant in the genomes of BRCA1-linked but not BRCA2-linked breast cancer. Here we define the mechanism underlying this rearrangement signature. We show that, in primary mammalian cells, BRCA1, but not BRCA2, suppresses the formation of tandem duplications at a site-specific chromosomal replication fork barrier imposed by the binding of Tus proteins to an array of Ter sites. BRCA1 has no equivalent role at chromosomal double-stranded DNA breaks, indicating that tandem duplications form specifically at stalled forks. Tandem duplications in BRCA1 mutant cells arise by a replication restart-bypass mechanism terminated by end joining or by microhomology-mediated template switching, the latter forming complex tandem duplication breakpoints. Solitary DNA ends form directly at Tus-Ter, implicating misrepair of these lesions in tandem duplication formation. Furthermore, BRCA1 inactivation is strongly associated with ~10 kilobase tandem duplications in ovarian cancer. This tandem duplicator phenotype may be a general signature of BRCA1-deficient cancer. Nature 2017 Nov 30; 551(7682):590-595

The Contribution of Urban Foodways to Health Disparities

How do urban food environments produce health disparities? The literature currently emphasizes the etiologic relevance of urban food deserts and their nutritional shortcomings. This paper instead examines the health relevance of foodways—the social dynamics surrounding the production, purchase, and consumption of food. We report on data from 32 photo-elicitation interviews conducted with adult residents of Philadelphia, examining distinct foodways and health concerns that play out in the most commonly discussed retail establishments: corner stores, “Stop and Go’s” (delis that also sell beer), and Chinese takeout restaurants. Corner store visits, described as a routinized element of children’s school day, were implicated in early life patterning of unsound nutritional choices. Stop and Go’s were described as a health threat because of their alcohol sales and tacit promotion of public drunkenness, coupled with accessibility to youth. Stop and Go’s and Chinese takeouts both were perceived as generators of violence in part because of on-site sales of alcohol, drug paraphernalia, and illicit drugs. Chinese takeouts also were described as symbolic reminders of African Americans’ economic exclusion and as places infused with race/ethnic tension and hostile merchant–customer interactions. Instead of viewing the food environment simply as a source of calories and nutrients, participants discussed the complex social dynamics that play out therein, raising a range of important considerations for (especially disadvantaged) urban residents’ safety, physical well-being, and mental health