Journal Article

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

Abraham, Karan J., Damaren, Christopher J., Chung, Daniel K. C., Chan, Janet N. Y., Strecker, Jonathan, Mekhail, Karim, Oshidari, Roxanne

2018

Overview

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. Following DNA damage, different processes come to action to aid repair. The authors here find that microtubule filaments within the cell nucleus capture and non-randomly mobilize damaged chromatin to mediate DNA repair.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14 / 14/19 / 14/63 / 631/208/211 / 631/326/193 / 631/57/343/2280 / 631/80/386/1700 / 631/80/386/1899 / Cell Cycle Proteins - metabolism / Cell Nucleus - metabolism / Chromatin / Chromatin - metabolism / Damage / Deoxyribonucleic acid / DNA / DNA damage / DNA Damage - physiology / DNA repair / DNA Repair - physiology / Filaments / Humanities and Social Sciences / Intravital Microscopy / Kinesin / Lesions / Macromolecules / Microtubule-Associated Proteins - metabolism / Microtubules / Microtubules - metabolism / Mobility / multidisciplinary / Rad9 protein / Repair / Saccharomyces cerevisiae - physiology / Saccharomyces cerevisiae Proteins - metabolism / Science / Science (multidisciplinary)