DOI: 10.1101/498808Dec 17, 2018Paper

PLK1 protects centromeres from BLM-mediated disintegration to promote chromosome biorientation

BioRxiv : the Preprint Server for Biology
Owen Addis JonesKok-Lung Chan


Faithful chromosome segregation cannot be achieved without proper chromosome biorientation (so-called metaphase alignment). Disabling PLK1, a key mitotic kinase, impairs multiple aspects of mitosis, particularly chromosome alignment. This is believed primarily due to unstable bipolar spindle-kinetochore attachments. Contrary to this belief, PLK1 inactivation does not necessarily abolish metaphase establishment, instead impairing its maintenance. Here, we demonstrate that the failure of chromosome biorientation maintenance is driven by a hitherto undescribed mechanism named centromere dislocation. Without an active PLK1 during mitosis, BLM helicase is illegitimately recruited to and unwinds a specific centromere domain underneath kinetochores in a PICH-dependent manner, impairing centromere configuration and rigidity. Acting with bipolar spindle pulling forces, the distorted centromeric chromatin is promptly converted into an ultra-thin DNA structure, termed pre-anaphase interchromatin DNA threads(PITs) and fails to withstand spindle tension, resulting in whole-chromosome arms splitting. This devastating dechromatinisation action severely damages the centromere integrity and destroys normal metaphase maintenance. Therefore, our ...Continue Reading

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