How Cells Respond to DNA Breaks in Mitosis

Andrew N Blackford; Manuel Stucki

doi:10.1016/j.tibs.2019.12.010

How Cells Respond to DNA Breaks in Mitosis

Trends Biochem Sci. 2020 Apr;45(4):321-331. doi: 10.1016/j.tibs.2019.12.010. Epub 2020 Jan 27.

Authors

Andrew N Blackford¹, Manuel Stucki²

Affiliations

¹ Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Cancer Research UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: andrew.blackford@imm.ox.ac.uk.
² Department of Gynecology, University of Zurich, Wagistrasse 14, CH-8952 Schlieren, Switzerland. Electronic address: Manuel.Stucki@usz.ch.

PMID: 32001093
DOI: 10.1016/j.tibs.2019.12.010

Abstract

DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to chromosomal instability if they are not repaired correctly. DSBs are especially dangerous in mitosis when cells go through the complex process of equal chromosome segregation into daughter cells. When cells encounter DSBs in interphase, they are able to arrest the cell cycle until the breaks are repaired before entering mitosis. However, when DSBs occur during mitosis, cells no longer arrest but prioritize completion of cell division over repair of DNA damage. This review focuses on recent progress in our understanding of the mechanisms that allow mitotic cells to postpone DSB repair without accumulating massive chromosomal instability. Additionally, we review possible physiological consequences of failed DSB responses in mitosis.

Keywords: DNA double-strand breaks; cell-cycle checkpoints; chromosomal instability; chromothripsis; micronuclei; mitosis.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cells / metabolism*
DNA Breaks, Double-Stranded
DNA Damage
Humans
Mitosis*

Grants and funding

20772/CRUK_/Cancer Research UK/United Kingdom