ROS and Oxidative Stress Are Elevated in Mitosis during Asynchronous Cell Cycle Progression and Are Exacerbated by Mitotic Arrest

Jesse C Patterson; Brian A Joughin; Bert van de Kooij; Daniel C Lim; Douglas A Lauffenburger; Michael B Yaffe

doi:10.1016/j.cels.2019.01.005

ROS and Oxidative Stress Are Elevated in Mitosis during Asynchronous Cell Cycle Progression and Are Exacerbated by Mitotic Arrest

Cell Syst. 2019 Feb 27;8(2):163-167.e2. doi: 10.1016/j.cels.2019.01.005. Epub 2019 Feb 20.

Authors

Jesse C Patterson¹, Brian A Joughin², Bert van de Kooij¹, Daniel C Lim¹, Douglas A Lauffenburger³, Michael B Yaffe⁴

Affiliations

¹ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁴ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: myaffe@mit.edu.

Abstract

Although elevated levels of reactive oxygen species (ROS) have been observed in cancer cells and cancer cells aberrantly proliferate, it is not known whether the level of reactive oxygen species and the accumulation of oxidative damage to macromolecules vary across the cell cycle. Here, we measure the prevalence of reactive oxygen species and of biomolecule oxidation across the cell cycle in freely cycling cancer cells. We report that reactive oxygen species vary during the cell cycle and peak in mitosis, resulting in mitotic accumulation of oxidized protein cysteine residues. Prolonged mitotic arrest further increased the levels of ROS and the abundance of oxidatively damaged biomolecules, including cysteine-sulfenic-acid-containing proteins and 8-oxoguanine. These finding suggest that mitotic arrest agents may enhance the effects of ROS-dependent anticancer therapies.

Keywords: 8-oxoguanine; ROS; antimitotic cancer therapy; cell cycle; docetaxel; mitosis; mitotic arrest; oxidative DNA damage; protein cysteine oxidation; reactive oxygen species.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cell Cycle / genetics*
Humans
Mitosis
Oxidative Stress
Reactive Oxygen Species / metabolism*

Substances

Reactive Oxygen Species

Abstract

Publication types

MeSH terms

Substances

Grants and funding