Histone stress: an unexplored source of chromosomal instability in cancer?

Abstract

Ploidy is stably maintained in most human somatic cells by a sequential and tight coordination of cell cycle events. Undesired whole genome doublings or duplications are frequent in tumours and have been quite recently described as macro-evolutionary events associated with poor prognosis. In vitro and in vivo studies suggest that polyploidy can favour genome instability, facilitate the formation and progression of tumours, and modify their sensitivity to chemotherapeutic agents. Stress is strongly related to changes in ploidy and whole genome doublings. In this review, we summarize different mechanisms that promote polyploidization, describe a new type of stress able to trigger WGDs in S. cerevisiae, histone stress, and provide some examples and theoretical scenarios that support that cancer cells might suffer from this type of stress. We finally highlight some results showing that the kinase Swe1 (Wee1 in humans) has a role in sensing histone levels before cells enter mitosis, thereby avoiding their undesired consequences on chromosome segregation and ploidy control.

Keywords: Cancer; Genome instability; Histones; Polyploidy; Swe1; Whole genome duplication.