A checkpoint-independent mechanism delays entry into mitosis after UV irradiation

Author:

Rothe Christiane1,Rødland Gro Elise1,Anda Silje1,Stonyte Vilte12,Boye Erik1,Lopez-Aviles Sandra2,Grallert Beáta1ORCID

Affiliation:

1. Department of Radiation Biology; Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway

2. Centre for Molecular Medicine Norway, University of Oslo, Gaustadalléen 21, 0349 Oslo, Norway

Abstract

When cells are exposed to stress they delay entry into mitosis. The most extensively studied mechanism behind this delay is the DNA-damage-induced G2/M checkpoint. Here, we show the existence of an additional stress-response pathway which is independent of the classic ATR/Rad3-dependent checkpoint. This novel mechanism delays entry mitosis independent of the spindle assembly checkpoint and the mitotic kinases Fin1, Ark1 and Plo1. The pathway delays activation of the mitotic CDK, Cdc2, after UV irradiation. Furthermore, we demonstrate that translation of the mitotic cyclin Cdc13 is selectively downregulated after UV-irradiation and we propose that this downregulation of Cdc13 contributes to the delayed activation of Cdc2 and the delayed mitosis.

Funder

Helse Sør-Øst RHF

Radiumhospitalets Legater

Fougner Hartmanns Familiefond

Publisher

The Company of Biologists

Subject

Cell Biology

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