Environmental Stress Induces Trinucleotide Repeat Mutagenesis in Human Cells by Alt-Nonhomologous End Joining Repair
JOURNAL OF MOLECULAR BIOLOGY
Authors: Chatterjee, Nimrat; Lin, Yunfu; Yotnda, Patricia; Wilson, John H.
Abstract
Multiple pathways modulate the dynamic mutability of trinucleotide repeats (TNRs), which are implicated in neurodegenerative disease and evolution. Recently, we reported that environmental stresses induce TNR mutagenesis via stress responses and rereplication, with more than 50% of mutants carrying deletions or insertions-molecular signatures of DNA double-strand break repair. We now show that knockdown of alt-nonhomologous end joining (alt-NHEJ) components-XRCC1, LIG3, and PARP1-suppresses stress-induced TNR mutagenesis, in contrast to the components of homologous recombination and NHEJ, which have no effect. Thus, alt-NHEJ, which contributes to genetic mutability in cancer cells, also plays a novel role in environmental stress-induced TNR mutagenesis. Published by Elsevier Ltd.
An Examination of an Iconic Trap-Neuter-Return Program: The Newburyport, Massachusetts Case Study
ANIMALS
Authors: Spehar, Daniel D.; Wolf, Peter J.
Abstract
The use of trap-neuter-return (TNR) as a humane alternative to the lethal management of free-roaming cats has been on the rise for several decades in the United States; however a relative paucity of data from TNR programs exists. An iconic community-wide TNR effort; initiated in 1992 and renowned for having eliminated hundreds of free-roaming cats from the Newburyport; Massachusetts waterfront; is cited repeatedly; yet few details appear in the literature. Although the presence of feline population data was quite limited; a detailed narrative emerged from an examination of contemporaneous reports; extant TNR program documents; and stakeholder testimony. Available evidence indicates that an estimated 300 free-roaming cats were essentially unmanaged prior to the commencement of the TNR program; a quick reduction of up to one-third of the cats on the waterfront was attributed to the adoption of sociable cats and kittens; the elimination of the remaining population; over a 17-year period; was ascribed to attrition. These findings illuminate the potential effectiveness of TNR as a management practice; as well as call attention to the need for broad adoption of systematic data collection and assessment protocols.