APOBEC3G rescues cells from the deleterious effects of DNA damage

Alexander Botvinnik, Pushkar Shivam, Yoav Smith, Gunjan Sharma, Udy Olshevsky, Ofra Moshel, Zakhariya Manevitch, Nuria Climent, Harold Oliva, Elena Britan-Rosich, Moshe Kotler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (hA3G), a member of the APOBEC family, was described as an anti-HIV-1 restriction factor, deaminating reverse transcripts of the HIV-1 genome. Several types of cancer cells that express high levels of A3G, such as diffuse large B-cell lymphoma cells and glioblastomas, show enhanced cell survival after ionizing radiation and chemotherapy treatments. Previously, we showed that hA3G promotes (DNA) double-strand breaks repair in cultured cells and rescues transgenic mice from a lethal dose of ionizing radiation. Here, we show that A3G rescues cells from the detrimental effects of DNA damage induced by ultraviolet irradiation and by combined bromodeoxyuridine and ultraviolet treatments. The combined treatments stimulate the synthesis of cellular proteins, which are exclusively associated with A3G expression. These proteins participate mainly in nucleotide excision repair and homologous recombination DNA repair pathways. Our results implicate A3G inhibition as a potential strategy for increasing tumor cell sensitivity to genotoxic treatments.

Original languageAmerican English
Pages (from-to)6063-6077
Number of pages15
JournalFEBS Journal
Volume288
Issue number20
DOIs
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 Federation of European Biochemical Societies

Keywords

  • DNA repair
  • UV irradiation
  • cytidine deaminases
  • radiation resistance

Fingerprint

Dive into the research topics of 'APOBEC3G rescues cells from the deleterious effects of DNA damage'. Together they form a unique fingerprint.

Cite this