Summary The body’s first line of defense against environmental assaults, the skin barrier is maintained by epithelial stem cells (EpSCs). Despite EpSCs’ vulnerability to inflammatory pressures, neither the primary response nor its enduring consequences are understood. Here, we unearth a prolonged memory to acute inflammation that enables EpSCs to hasten barrier restoration following subsequent tissue damage. This functional adaptation does not require skin resident macrophages or T cells. Rather, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fueling this memory is Aim2, encoding an activator of the inflammasome. Absence of AIM2 or its downstream effectors, Caspase-1 and Interleukin-1β, erases EpSCs’ ability to recollect inflammation. While EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity likely increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.

Summary Premature anaphase onset is prevented by the mitotic checkpoint through production of a “wait anaphase” inhibitor(s) that blocks recognition of cyclin B and securin by Cdc20-activated APC/C, an E3 ubiquitin ligase which targets them for destruction. Using physiologically-relevant levels of Mad2, Bub3, BubR1, and Cdc20, we demonstrate that unattached kinetochores on purified chromosomes catalytically generate a diffusible Cdc20 inhibitor or inhibit Cdc20 already bound to APC/C. Furthermore, the chromosome-produced inhibitor requires both recruitment of Mad2 by Mad1 that is stably bound at unattached kinetochores and dimerization-competent Mad2. We show that purified chromosomes promote BubR1 binding to APC/C-Cdc20 by acting directly on Mad2, but not BubR1. Our results support a model in which immobilized Mad1/Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1.

Cep152, the orthologue of Drosophila Asterless, is a Plk4 target that functions with Plk4 in centriole assembly.