Help or hindrance: how do microtubule-based forces contribute to genome damage and repair?

Abstract:

:Forces generated by molecular motors and the cytoskeleton move the nucleus and genome during many cellular processes, including cell migration and division. How these forces impact the genome, and whether cells regulate cytoskeletal forces to preserve genome integrity is unclear. We recently demonstrated that, in budding yeast, mutants that stabilize the microtubule cytoskeleton cause excessive movement of the mitotic spindle and nucleus. We found that increased nuclear movement results in DNA damage and increased time to repair the damage through homology-directed repair. Our results indicate that nuclear movement impairs DNA repair through increased tension on chromosomes and nuclear deformation. However, the previous studies have shown genome mobility, driven by cytoskeleton-based forces, aids in homology-directed DNA repair. This sets up an apparent paradox, where genome mobility may prevent or promote DNA repair. Hence, this review explores how the genome is affected by nuclear movement and how genome mobility could aid or hinder homology-directed repair.

journal_name

Curr Genet

journal_title

Current genetics

authors

Estrem C,Moore JK

doi

10.1007/s00294-019-01033-2

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

303-311

issue

2

eissn

0172-8083

issn

1432-0983

pii

10.1007/s00294-019-01033-2

journal_volume

66

pub_type

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