DNA damage in mitosis: SOD1 delays anaphase onset.

Abstract

Unrepaired DNA double strand breaks (DSBs) can lead to genomic instability, carcinogenesis, or cell death; however, mitotic cells do not exhibit a DNA damage checkpoint delay and do not repair DSBs until the next cell cycle. Instead, DSBs can delay anaphase through the mitotic spindle checkpoint by an incompletely understood mechanism. Li et al. now show that, in human mitotic cells with damaged DNA, superoxide dismutase 1 inhibits protein phosphatase 2a, which dephosphorylates kinetochore proteins to silence the spindle checkpoint, leading to persistent spindle checkpoint activation and delayed anaphase onset. Here, the biological significance of these findings and open questions are discussed.