Cell cycle-independent furrowing triggered by phosphomimetic mutations of the INCENP STD motif requires Plk1

Timely and precise control of Aurora B kinase, the chromosomal passenger complex (CPC) catalytic subunit, is essential for accurate chromosome segregation and cytokinesis. Post-translational modifications of CPC subunits are directly involved in controlling Aurora B activity. Here, we identified a highly conserved acidic STD-rich motif of INCENP that is phosphorylated during mitosis in vivo and by Plk1 in vitro and is involved in controlling Aurora B activity. By using an INCENP conditional-knockout cell line, we show that impairing the phosphorylation status of this region disrupts chromosome congression and induces cytokinesis failure. In contrast, mimicking constitutive phosphorylation not only rescues cytokinesis but also induces ectopic furrows and contractile ring formation in a Plk1- and ROCK1-dependent manner independent of cell cycle and microtubule status. Our experiments identify the phospho-regulation of the INCENP STD motif as a novel mechanism that is key for chromosome alignment and cytokinesis.Publisher's Versio

A two-step mechanism for epigenetic specification of centromere identity and function

The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.National Institutes of Health grant: (GM 074150); Ludwig Institute for Cancer Research; European Molecular Biology Organization (EMBO) long-term fellowship

Listening for commissioning: A participatory study exploring young people's experiences, views and preferences of school-based sexual health and school nursing

Aims and objectives: To explore the experiences, views and preferences of young people aged 11-19 years regarding school-based sexual health and school nursing to inform commissioning and delivery for one local authority area in England during 2015. Background: Promoting sexual health for young people remains a challenging, even controversial, but important public health issue. Concerns regarding accessibility, acceptability and efficacy in school-based sexual health and school nursing are evident in the literature. Additionally, a complex public health policy context now governs the funding, provision and delivery of sexual health and school nursing, which potentially presents further challenges. Design: A qualitative, participatory design was used to explore sexual health and school nursing. Data were generated from 15 focus groups (n = 74), with young people aged 11-19 years, in educational-based settings in one local authority area in England. Results: The resultant themes of visibility in relation to sexual health education and school nursing revealed both the complex tensions in designing and delivering acceptable and appropriate sexual health services for young people and the significance of participatory approaches. Conclusion: Our study shows the importance of participatory approaches in working with young people to clearly identify what they want and need in relation to sexual health. The findings also confirm the ways in which school-based sexual health remains challenging but requires a theoretical and conceptual shift. This we argue must be underpinned by participatory approaches. Relevance to clinical practice: School nurses have always had a significant role to play in promoting positive sexual health for young people and they are exceptionally well placed to challenge the risk-based cultures that frequently dominate school-based sexual health. A shift of debates and practices towards the promotion of positive sexual health cultures though previously argued for now requires the active engagement and involvement of young people. Keywords: focus groups; health improvement; participatory; qualitative; school nursing; sex education; sexual health; young people