Perinuclear Tethers License Telomeric DSBs for a Broad Kinesin- and NPC-dependent DNA Repair Process

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Jul 25

PMID 26205667

Citations 46

Authors

Daniel K C Chung

Janet N Y Chan

Jonathan Strecker

Wei Zhang

Sasha Ebrahimi-Ardebili

Thomas Lu

Karan J Abraham

Daniel Durocher

Karim Mekhail

Affiliations

Soon will be listed here.

Abstract

DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved in this process remain unclear. Here, we show that the kinesin-14 motor protein complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error-prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical role in telomerase-independent telomere maintenance. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.

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