TY - JOUR
T1 - APOBEC3G rescues cells from the deleterious effects of DNA damage
AU - Botvinnik, Alexander
AU - Shivam, Pushkar
AU - Smith, Yoav
AU - Sharma, Gunjan
AU - Olshevsky, Udy
AU - Moshel, Ofra
AU - Manevitch, Zakhariya
AU - Climent, Nuria
AU - Oliva, Harold
AU - Britan-Rosich, Elena
AU - Kotler, Moshe
N1 - Publisher Copyright:
© 2021 Federation of European Biochemical Societies
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - DNA repair
KW - UV irradiation
KW - cytidine deaminases
KW - radiation resistance
UR - http://www.scopus.com/inward/record.url?scp=85107576239&partnerID=8YFLogxK
U2 - 10.1111/febs.16025
DO - 10.1111/febs.16025
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C2 - 33999509
AN - SCOPUS:85107576239
SN - 1742-464X
VL - 288
SP - 6063
EP - 6077
JO - FEBS Journal
JF - FEBS Journal
IS - 20
ER -