Interphase Microtubules Safeguard Mitotic Progression by Suppressing an Aurora B-Dependent Arrest Induced by DNA Replication Stress.

Abstract:

:The segregation of chromosomes is a critical step during cell division. This process is driven by the elongation of spindle microtubules and is tightly regulated by checkpoint mechanisms. It is unknown whether microtubules affect checkpoint responses as passive contributors or active regulators of the process. We show here that interphase microtubules are essential to temporally restrict the effects of DNA replication stress to S phase in Saccharomyces cerevisiae. Tubulin mutants hypersensitive to DNA damage experience a strong but delayed mitotic checkpoint arrest after exposure to genotoxic stress in S phase. This untimely arrest is dependent on the Aurora B kinase but, surprisingly, not on the DNA damage checkpoint. Impaired microtubule-kinetochore interaction is the apparent cause for this unusual phenotype. Collectively, our results reveal that core components of microtubules potentiate the detection of DNA lesions created in S phase, thereby suppressing untimely activation of mitotic checkpoints after DNA replication stress.

journal_name

Cell Rep

journal_title

Cell reports

authors

Laflamme G,Sim S,Leary A,Pascariu M,Vogel J,D'Amours D

doi

10.1016/j.celrep.2019.02.051

subject

Has Abstract

pub_date

2019-03-12 00:00:00

pages

2875-2889.e3

issue

11

issn

2211-1247

pii

S2211-1247(19)30230-X

journal_volume

26

pub_type

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