Nature Communications (Feb 2020)

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

  • Alejandro Álvarez-Quilón,
  • José Terrón-Bautista,
  • Irene Delgado-Sainz,
  • Almudena Serrano-Benítez,
  • Rocío Romero-Granados,
  • Pedro Manuel Martínez-García,
  • Silvia Jimeno-González,
  • Cristina Bernal-Lozano,
  • Cristina Quintero,
  • Lourdes García-Quintanilla,
  • Felipe Cortés-Ledesma

DOI
https://doi.org/10.1038/s41467-020-14638-w
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 14

Abstract

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The ATM kinase is a key regulator of the DNA damage response to double-strand breaks (DSBs) and its homozygous loss in patients predisposes to lymphoid malignancies. Here, the authors develop a Tdp2 −/− Atm −/− double-deficient mouse model to uncover topoisomerase II-induced DSBs as significant drivers of the genomic rearrangements that underpin these tumours.