APOBEC3G protects the genome of human cultured cells and mice from radiation-induced damage

Yelena Britan-Rosich, Jing Ma, Eran Kotler, Faizan Hassan, Alexander Botvinnik, Yoav Smith, Ofra Moshel, Abed Nasereddin, Gunjan Sharma, Eli Pikarsky, Susan Ross*, Moshe Kotler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Cytosine deaminases AID/APOBEC proteins act as potent nucleic acid editors, playing important roles in innate and adaptive immunity. However, the mutagenic effects of some of these proteins compromise genomic integrity and may promote tumorigenesis. Here, we demonstrate that human APOBEC3G (A3G), in addition to its role in innate immunity, promotes repair of double-strand breaks (DSBs) in vitro and in vivo. Transgenic mice expressing A3G successfully survived lethal irradiation, whereas wild-type controls quickly succumbed to radiation syndrome. Mass spectrometric analyses identified the differential upregulation of a plethora of proteins involved in DSB repair pathways in A3G-expressing cells early following irradiation to facilitate repair. Importantly, we find that A3G not only accelerates DSB repair but also promotes deamination-dependent error-free rejoining. These findings have two implications: (a) strategies aimed at inhibiting A3G may improve the efficacy of genotoxic therapies used to cure malignant tumours; and (b) enhancing A3G activity may reduce acute radiation syndrome in individuals exposed to ionizing radiation.

Original languageAmerican English
Pages (from-to)1822-1839
Number of pages18
JournalFEBS Journal
Volume290
Issue number7
DOIs
StatePublished - Apr 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Keywords

  • APOBEC3G
  • DNA damage response
  • DNA repair
  • cytidine deaminase
  • homologous recombination
  • mouse
  • non-homologous end joining

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