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In this Review, Hustedt and Durocher discuss recent advances in our understanding of how different repair pathways, in particular double-strand break repair, are regulated across the cell cycle to ensure faithful segregation of the genome.
Delineating the behaviour of haematopoietic stem cells (HSCs) in vivo has thus far proven challenging. Two studies in zebrafish and mouse models now track HSCs in vivo using fate mapping with multicolour approaches to provide further insights into clonal events that regulate blood development, HSC function and differentiation during homeostasis and stress conditions.
Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process, including a role for non-homologous end joining.
Cadherin adhesion complexes have recently emerged as sensors of tissue tension that regulate key developmental processes. Super-resolution microscopy experiments now unravel the spatial organization of the interface between cadherins and the actin cytoskeleton and reveal how vinculin, a central component in cadherin mechanotransduction, is regulated by mechanical and biochemical signals.
Henninger et al. analyse the early clonal events that underlie haematopoiesis and establish the number of stem cell clones that arise from the ventral dorsal aorta to maintain lifelong blood production.
Bertocchi and colleagues describe the organization of cadherin-based adhesions using super-resolution microscopy. They find that α-catenin is important for vinculin localization and observe a conformational change in vinculin following its activation.
Lin and colleagues report that hypoxia induces TRAF6-dependent mono-ubiquitylation of histone H2AX, which promotes binding and stabilization of HIF1α. Activated HIF1α signalling in turn promotes tumorigenesis and metastasis.
Resnik-Docampo et al. demonstrate that depletion of the tricellular junction protein Gliotactin in young flies leads to hallmarks of ageing, including an increase in intestinal stem cell proliferation and a block in terminal differentiation.
Daley and colleagues report that MAPK signalling controls pluripotency in embryonic stem cells and during somatic cell reprogramming by enhancing the stability and effects of LIN28 on direct mRNA targets through its phosphorylation by ERK.
Ly et al. establish a method to selectively inactivate the centromere of the Y chromosome to follow chromosome shattering and micronuclei formation through several cell cycles, and suggest re-ligation of chromosome fragments is dependent on non-homologous end joining.
