Lysosomes are membrane-surrounded cytoplasmic organelles filled with a powerful cocktail of hydrolases. Besides degrading cellular constituents inside the lysosomal lumen, lysosomal hydrolases promote tissue remodeling when delivered to the extracellular space and cell death when released to the cytosol. Here, we show that spatially and temporally controlled lysosomal leakage contributes to the accurate chromosome segregation in normal mammalian cell division. One or more chromatin-proximal lysosomes leak in the majority of prometaphases, after which active cathepsin B (CTSB) localizes to the metaphase chromatin and cleaves a small subset of histone H3. Stabilization of lysosomal membranes or inhibition of CTSB activity during mitotic entry results in a significant increase in telomere-related chromosome segregation defects, whereas cells and tissues lacking CTSB and cells expressing CTSB-resistant histone H3 accumulate micronuclei and other nuclear defects. These data suggest that lysosomal leakage and chromatin-associated CTSB contribute to proper chromosome segregation and maintenance of genomic integrity.

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For the first 30 minutes, a stillborn baby feels soft and warm, just like a live baby. The time immediately after birth can be seen as an “acute” situation – a time that can never be relived. After just 30 minutes, the baby will grow cold, and its colour will change. Following stillbirth, parents are in a state of shock, and asking whether they want to see and hold their baby may suggest that it is not obvious that they would want to do so. This creates doubt, and for many the spontaneous reaction may be to reply with a refusal they later regret. Not seeing the baby immediately after delivery also means not holding the baby immediately afterwards. Parents who have both seen and held the baby during the first 30 minutes describes this as the most valuable time they had with their baby.

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