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 Repjournal_title
Cell reportsauthors
Laflamme G,Sim S,Leary A,Pascariu M,Vogel J,D'Amours Ddoi
10.1016/j.celrep.2019.02.051subject
Has Abstractpub_date
2019-03-12 00:00:00pages
2875-2889.e3issue
11issn
2211-1247pii
S2211-1247(19)30230-Xjournal_volume
26pub_type
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