A New Mode of Mitotic Surveillance

Bramwell G. Lambrus, Andrew Holland

Research output: Contribution to journalArticle

Abstract

Cells have evolved certain precautions to preserve their genomic content during mitosis and avoid potentially oncogenic errors. Besides the well-established DNA damage checkpoint and spindle assembly checkpoint (SAC), recent observations have identified an additional mitotic failsafe referred to as the mitotic surveillance pathway. This pathway triggers a cell cycle arrest to block the growth of potentially unfit daughter cells and is activated by both prolonged mitosis and centrosome loss. Recent genome-wide screens surprisingly revealed that 53BP1 and USP28 act upstream of p53 to mediate signaling through the mitotic surveillance pathway. Here we review advances in our understanding of this failsafe and discuss how 53BP1 and USP28 adopt noncanonical roles to function in this pathway. Cells have developed quality control mechanisms to protect genome integrity in mitosis.Cells can trigger cell cycle arrest in response to delayed mitosis or centrosome loss.This response is p53 dependent but independent of known p53-activating signaling pathways, suggesting the existence of a novel 'mitotic surveillance pathway'.Genome-wide screens reveal that 53BP1 and USP28 activate p53 in this surveillance response.The 53BP1-USP28-p53 axis may serve as a form of mitotic quality control by preventing the growth of cells that have an increased chance of making mitotic errors.

Original languageEnglish (US)
JournalTrends in Cell Biology
DOIs
Publication statusAccepted/In press - 2017

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ASJC Scopus subject areas

  • Cell Biology

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