Overlapping roles for PLK1 and Aurora A during meiotic centrosome biogenesis in mouse spermatocytes.

The establishment of bipolar spindles during meiotic divisions ensures faithful chromosome segregation to prevent gamete aneuploidy. We analyzed centriole duplication, as well as centrosome maturation and separation during meiosis I and II using mouse spermatocytes. The first round of centriole duplication occurs during early prophase I, and then, centrosomes mature and begin to separate by the end of prophase I to prime formation of bipolar metaphase I spindles. The second round of centriole duplication occurs at late anaphase I, and subsequently, centrosome separation coordinates bipolar segregation of sister chromatids during meiosis II. Using a germ cell-specific conditional knockout strategy, we show that Polo-like kinase 1 and Aurora A kinase are required for centrosome maturation and separation prior to metaphase I, leading to the formation of bipolar metaphase I spindles. Furthermore, we show that PLK1 is required to block the second round of centriole duplication and maturation until anaphase I. Our findings emphasize the importance of maintaining strict spatiotemporal control of cell cycle kinases during meiosis to ensure proficient centrosome biogenesis and, thus, accurate chromosome segregation during spermatogenesis.

PLK1 depletion alters homologous recombination and synaptonemal complex disassembly events during mammalian spermatogenesis.

Homologous recombination (HR) is an essential meiotic process that contributes to the genetic variation of offspring and ensures accurate chromosome segregation. Recombination is facilitated by the formation and repair of programmed DNA double-strand breaks. These DNA breaks are repaired via recombination between maternal and paternal homologous chromosomes and a subset result in the formation of crossovers. HR and crossover formation is facilitated by synapsis of homologous chromosomes by a proteinaceous scaffold structure known as the synaptonemal complex (SC). Recent studies in yeast and worms have indicated that polo-like kinases (PLKs) regulate several events during meiosis, including DNA recombination and SC dynamics. Mammals express four active PLKs (PLK1-4), and our previous work assessing localization and kinase function in mouse spermatocytes suggested that PLK1 coordinates nuclear events during meiotic prophase. Therefore, we conditionally mutated Plk1 in early prophase spermatocytes and assessed stages of HR, crossover formation, and SC processes. Plk1 mutation resulted in increased RPA foci and reduced RAD51/DMC1 foci during zygonema, and an increase of both class I and class II crossover events. Furthermore, the disassembly of SC lateral elements was aberrant. Our results highlight the importance of PLK1 in regulating HR and SC disassembly during spermatogenesis.

The impact of state fire safe cigarette policies on fire fatalities, injuries, and incidents.

Cigarettes are a leading cause of civilian deaths in home fires. Over the last decade, state fire service leaders and allied interest groups succeeded in persuading state lawmakers to require manufacturers to sell only low-ignition strength or "fire safe" cigarettes as a strategy to reduce these fatalities and the injuries and losses that stem from them. This article examines whether the states' fire safe cigarette laws actually helped to save lives, prevent injuries, and reduce the incidence of home fires ignited by cigarettes left unattended by smokers. Controlling for the effects of key demographic, social, economic, and housing variables, this study finds that the states' fire-safe cigarette policies had significant impacts on reducing the rate of smoking-related civilian fire deaths and the incidence of fires started by tobacco products. The findings also suggest that the states' fire safe cigarette policies may have helped to reduce the rate of smoking-related fire injuries. The study shows that collective actions by leaders in the fire service across the states can result in meaningful policy change that protects lives and advances public safety even when a political consensus for action is absent at the national level.