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载脂蛋白B mRNA编辑酶催化多肽样蛋白3C（APOBEC3C）是一种由基因毒素诱导产生的核仁蛋白，它被排除在DNA损伤位点之外。

APOBEC3C, a nucleolar protein induced by genotoxins, is excluded from DNA damage sites.

作者信息

Constantin Daniel, Dubuis Gilles, Conde-Rubio María Del Carmen, Widmann Christian

机构信息

Department of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Switzerland.

出版信息

FEBS J. 2022 Feb;289(3):808-831. doi: 10.1111/febs.16202. Epub 2021 Oct 4.

DOI:10.1111/febs.16202
PMID:34528388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9292673/
Abstract

The human genome contains 11 APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) cytidine deaminases classified into four families. These proteins function mainly in innate antiviral immunity and can also restrict endogenous retrotransposable element multiplication. The present study focuses on APOBEC3C (A3C), a member of the APOBEC3 subfamily. Some APOBEC3 proteins use their enzymatic activity on genomic DNA, inducing mutations and DNA damage, while other members facilitate DNA repair. Our results show that A3C is highly expressed in cells treated with DNA-damaging agents. Its expression is regulated by p53. Depletion of A3C slightly decreases proliferation and does not affect DNA repair via homologous recombination or nonhomologous end joining. The A3C interactomes obtained from control cells and cells exposed to the genotoxin etoposide indicated that A3C is a nucleolar protein. This was confirmed by the detection of either endogenous or ectopic A3C in nucleoli. Interestingly, we show that A3C is excluded from areas of DNA breaks in live cells. Our data also indicate that the C-terminal part of A3C is responsible for its nucleolar localization and exclusion from DNA damage sites.

摘要

人类基因组包含11种载脂蛋白B mRNA编辑催化多肽样（APOBEC）胞苷脱氨酶，分为四个家族。这些蛋白质主要在先天性抗病毒免疫中发挥作用，也可以限制内源性逆转录转座元件的增殖。本研究聚焦于APOBEC3亚家族成员之一的APOBEC3C（A3C）。一些APOBEC3蛋白对基因组DNA发挥酶活性，诱导突变和DNA损伤，而其他成员则促进DNA修复。我们的结果表明，A3C在经DNA损伤剂处理的细胞中高表达。其表达受p53调控。A3C的缺失会轻微降低细胞增殖，且不影响通过同源重组或非同源末端连接进行的DNA修复。从对照细胞和暴露于基因毒素依托泊苷的细胞中获得的A3C相互作用组表明，A3C是一种核仁蛋白。在核仁中检测到内源性或异位A3C证实了这一点。有趣的是，我们发现在活细胞中A3C被排除在DNA断裂区域之外。我们的数据还表明，A3C的C末端部分负责其核仁定位以及从DNA损伤位点的排除。

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