Nuclear cytochrome c – a mitochondrial visitor regulating damaged chromatin dynamics

Over the past decade, evidence has emerged suggesting a broader role for cytochrome c (Cyt c ) in programmed cell death. Recently, we demonstrated the ability of Cyt c to inhibit the nucleosome assembly activity of histone chaperones SET/template‐activating factor Iβ and NAP1‐related protein during DNA damage in humans and plants respectively. Here, we hypothesise a dual concentration‐dependent function for nuclear Cyt c in response to DNA damage. We propose that low levels of highly cytotoxic DNA lesions – such as double‐strand breaks – induce nuclear translocation of Cyt c , leading to the attenuation of nucleosome assembly and, thereby, increasing the time available for DNA repair. If DNA damage persists or is exacerbated, the nuclear Cyt c concentration would exceed a given threshold, causing the haem protein to block DNA remodelling altogether.