Chromatin Bridges: resolution, breakage or cytokinesis failure

Genome instability is a hallmark of cancer, intricately tied to tumor evolution. Chromatin bridges, aberrant DNA structures appearing during the last steps of cell division, are recognised contributors to genome instability, yet the extent of their implication in this process, as well as their significance in human tumors, remains unclear. Recent discoveries identified Topoisomerase-2-alpha (Top2α) as a key player in the detection of chromatin bridges and in the activation of the abscission checkpoint. This checkpoint delays abscission and stabilises the intercellular bridge, promoting the resolution of chromatin bridges. When chromatin bridges arise but fail to be detected and resolved, cytokinesis is compromised, leading to extensive DNA alterations in the daughter cells. These alterations, inherited by subsequent generations, fuel further genome instability. In this context, mutations in Charged Multivesicular Body Protein 4C (CHMP4C), member of the abscission checkpoint which actively participates in the abscission delay, were found to predispose to several types of cancer. Thus, the impact of chromatin bridges on genome stability is dependent on the efficacy of their management. The abscission checkpoint guides cells with chromatin bridges towards their resolution; however inefficient checkpoint function leads to cytokinesis failure and, consequently, genomic instability, which promotes tumour evolution.