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APOBEC3G rescues cells from the deleterious effects of DNA damage
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-05-17 , DOI: 10.1111/febs.16025
Alexander Botvinnik 1 , Pushkar Shivam 1 , Yoav Smith 2 , Gunjan Sharma 1 , Udy Olshevsky 1 , Ofra Moshel 3 , Zakhariya Manevitch 4 , Nuria Climent 5 , Harold Oliva 6 , Elena Britan-Rosich 1 , Moshe Kotler 1
The FEBS Journal ( IF 5.5 ) Pub Date : 2021-05-17 , DOI: 10.1111/febs.16025
Alexander Botvinnik 1 , Pushkar Shivam 1 , Yoav Smith 2 , Gunjan Sharma 1 , Udy Olshevsky 1 , Ofra Moshel 3 , Zakhariya Manevitch 4 , Nuria Climent 5 , Harold Oliva 6 , Elena Britan-Rosich 1 , Moshe Kotler 1
Affiliation
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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.
中文翻译：
APOBEC3G 从 DNA 损伤的有害影响中拯救细胞
人类载脂蛋白 B mRNA 编辑酶、催化多肽样 3G (hA3G) 是 APOBEC 家族的成员，被描述为抗 HIV-1 限制因子，可对 HIV-1 基因组的逆转录物脱氨基。几种表达高水平 A3G 的癌细胞，例如弥漫性大 B 细胞淋巴瘤细胞和胶质母细胞瘤，在电离辐射和化学疗法治疗后显示出增强的细胞存活率。以前，我们表明 hA3G 可促进培养细胞中的 (DNA) 双链断裂修复，并将转基因小鼠从致死剂量的电离辐射中拯救出来。在这里，我们展示了 A3G 从紫外线照射和溴脱氧尿苷和紫外线联合治疗引起的 DNA 损伤的有害影响中拯救细胞。联合治疗刺激细胞蛋白质的合成，与 A3G 表达完全相关。这些蛋白质主要参与核苷酸切除修复和同源重组 DNA 修复途径。我们的结果暗示 A3G 抑制是增加肿瘤细胞对基因毒性治疗敏感性的潜在策略。
更新日期：2021-05-17
中文翻译：
APOBEC3G 从 DNA 损伤的有害影响中拯救细胞
人类载脂蛋白 B mRNA 编辑酶、催化多肽样 3G (hA3G) 是 APOBEC 家族的成员，被描述为抗 HIV-1 限制因子，可对 HIV-1 基因组的逆转录物脱氨基。几种表达高水平 A3G 的癌细胞，例如弥漫性大 B 细胞淋巴瘤细胞和胶质母细胞瘤，在电离辐射和化学疗法治疗后显示出增强的细胞存活率。以前，我们表明 hA3G 可促进培养细胞中的 (DNA) 双链断裂修复，并将转基因小鼠从致死剂量的电离辐射中拯救出来。在这里，我们展示了 A3G 从紫外线照射和溴脱氧尿苷和紫外线联合治疗引起的 DNA 损伤的有害影响中拯救细胞。联合治疗刺激细胞蛋白质的合成，与 A3G 表达完全相关。这些蛋白质主要参与核苷酸切除修复和同源重组 DNA 修复途径。我们的结果暗示 A3G 抑制是增加肿瘤细胞对基因毒性治疗敏感性的潜在策略。
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