Research Papers:

Nuclear myosin/actin-motored contact between homologous chromosomes is initiated by ATM kinase and homology-directed repair proteins at double-strand DNA breaks to suppress chromosome rearrangements

Viktoria N. Evdokimova, Manoj Gandhi, Alyaksandr V. Nikitski, Christopher J. Bakkenist and Yuri E. Nikiforov _

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Oncotarget. 2018; 9:13612-13622. https://doi.org/10.18632/oncotarget.24434

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Viktoria N. Evdokimova1,*, Manoj Gandhi1,*, Alyaksandr V. Nikitski1, Christopher J. Bakkenist2 and Yuri E. Nikiforov1

1Department of Pathology, University of Pittsburgh, Pittsburgh, PA, 15213, USA

2Department of Radiation Oncology and Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15232, USA

*These authors have contributed equally to this work

Correspondence to:

Yuri E. Nikiforov, email: nikiforovye@upmc.edu

Keywords: chromosome; double-strand break; ATM; nuclear motors; DNA repair

Received: November 30, 2017    Accepted: January 30, 2018    Published: February 07, 2018


We provide evidence for a mechanism of DNA repair that requires nuclear myosin/actin-dependent contact between homologous chromosomes to prevent formation of chromosomal rearrangement in human cells. We recently showed that DNA double strand breaks (DSBs) induced by γ-rays or endonucleases cause ATM-dependent contact formation between homologous chromosomes at damaged sites of transcriptionally active chromatin in G0/G1-phase cells. Here, we report that the mechanism of contact generation between homologous chromosomes also requires homology-directed repair proteins, including BRCA1, RAD51 and RAD52, and nuclear myosin/actin-motors. Moreover, inhibition of ATM kinase or deficiency in nuclear actin polymerization causes carcinogenic RET/PTC chromosome rearrangements after DSBs induction in human cells. These data suggest that DSBs in transcriptionally active euchromatin in G0/G1-phase cells are repaired through a mechanism that requires contact formation between homologous chromosomes and that this mechanism is mediated by HDR proteins and nuclear myosin/actin motors.

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