Tipping the balance in histone supply puts genome stability at stake.

Specific localization of the histone H3 variant CENP-A at centromeres is key for faithful chromosome segregation during cell division, with CENP-A mislocalization being associated with chromosomal instability and cancer. New work in identifies the H3-H4 chaperone DNAJC9 as a factor restricting CENP-A localization, underscoring the importance of balancing H3 and CENP-A histone levels for ensuring proper CENP-A localization and maintaining genome stability.

CENP-A Regulation and Cancer.

In mammals, CENP-A, a histone H3 variant found in the centromeric chromatin, is critical for faithful chromosome segregation and genome integrity maintenance through cell divisions. Specifically, it has dual functions, enabling to define epigenetically the centromere position and providing the foundation for building up the kinetochore. Regulation of its dynamics of synthesis and deposition ensures to propagate proper centromeres on each chromosome across mitosis and meiosis.

CENP-A overexpression promotes distinct fates in human cells, depending on p53 status.

Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear.