Nuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair

Roxanne Oshidari, Jonathan Strecker, Daniel K. C. Chung, Karan J. Abraham, Janet N. Y. Chan, Christopher J. Damaren and Karim Mekhail ()
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Roxanne Oshidari: University of Toronto
Jonathan Strecker: University of Toronto
Daniel K. C. Chung: University of Toronto
Karan J. Abraham: University of Toronto
Janet N. Y. Chan: University of Toronto
Christopher J. Damaren: University of Toronto
Karim Mekhail: University of Toronto

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Damaged DNA shows increased mobility, which can promote interactions with repair-conducive nuclear pore complexes (NPCs). This apparently random mobility is paradoxically abrogated upon disruption of microtubules or kinesins, factors that typically cooperate to mediate the directional movement of macromolecules. Here, we resolve this paradox by uncovering DNA damage-inducible intranuclear microtubule filaments (DIMs) that mobilize damaged DNA and promote repair. Upon DNA damage, relief of centromeric constraint induces DIMs that cooperate with the Rad9 DNA damage response mediator and Kar3 kinesin motor to capture DNA lesions, which then linearly move along dynamic DIMs. Decreasing and hyper-inducing DIMs respectively abrogates and hyper-activates repair. Accounting for DIM dynamics across cell populations by measuring directional changes of damaged DNA reveals that it exhibits increased non-linear directional behavior in nuclear space. Abrogation of DIM-dependent processes or repair-promoting factors decreases directional behavior. Thus, inducible and dynamic nuclear microtubule filaments directionally mobilize damaged DNA and promote repair.

Date: 2018
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DOI: 10.1038/s41467-018-05009-7

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