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This Week in Cell: Jun 28, 2017

Researchers from St. Jude Children's Research Hospital describe apparent ties between de novo DNA methylation and T cell exhaustion. Using whole-genome bisulfite sequencing, the team profiled methylation patterns in antigen-specific mouse CD8 T cells at different stages of immune response after activation. In the process, they detected genome-wide methylation programs that seemed to mount with time after activation, leading to diminished T cell expansion and clonal diversity during treatment with immune checkpoint blockade treatment targeting PD-1. Blocking this methylation, on the other hand, the authors were able to staunch T cell exhaustion and boost T cell responses in the mouse CD8 T cells.

A team from the US and UK profiles DNA polymerase activity on leading and lagging strand DNA synthesis, along with other replication features, in individual replisomes in Escherichia coli. The researchers relied on a rolling-circle assay, coupled with single-molecule microscopy, to document independent polymerase functions on leading and lagging strands and other replisome dynamics. Based on their findings, the author "conclude that the stochastic behavior of replisome components ensures complete DNA duplication without requiring coordination of leading- and lagging-strand synthesis." The Scan covered their video here.

Investigators from Baylor College of Medicine and the University of Texas Health Center at Houston report on E. coli genes that appear to enhance longevity in the worm model Caenorhabditis elegans. Using an E. coli single gene knockout library, the team screened for bacterial genes that boost or reduce C. elegans lifespan when consumed by the worm. The search led to more than two-dozen bacterial gene knockouts that appeared to dial up longevity in C. elegans, prompting follow-up experiments that offered a clearer look at the altered pathways and product secretions by the pro-longevity bugs. "Together," the study's authors say, "our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity."