Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
J Genet Genomics. 2017 Sep 20;44(9):423-437. doi: 10.1016/j.jgg.2017.04.009. Epub 2017 Aug 7.
APOBECs (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) are a family of cytidine deaminases that prefer single-stranded nucleic acids as substrates. Besides their physiological functions, APOBEC family members have been found to cause hypermutations of cancer genomes, which could be correlated with cancer development and poor prognosis. Recently, APOBEC family members have been combined with the versatile CRISPR/Cas9 system to perform targeted base editing or induce hypermutagenesis. This combination improved the CRISPR/Cas9-mediated gene editing at single-base precision, greatly enhancing its usefulness. Here, we review the physiological functions and structural characteristics of APOBEC family members and their roles as endogenous mutators that contribute to hypermutations during carcinogenesis. We also review the various iterations of the APOBEC-CRISPR/Cas9 gene-editing tools, pointing out their features and limitations as well as the possibilities for future developments.
载脂蛋白 B mRNA 编辑酶催化多肽样物（APOBECs）是一类胞嘧啶脱氨酶，它们优先以单链核酸为底物。除了其生理功能外，还发现 APOBEC 家族成员可导致癌症基因组的超突变，这可能与癌症的发展和预后不良有关。最近，APOBEC 家族成员与多功能的 CRISPR/Cas9 系统结合，以进行靶向碱基编辑或诱导超突变。这种组合提高了 CRISPR/Cas9 介导的单碱基精度的基因编辑，大大增强了其有用性。在这里，我们回顾了 APOBEC 家族成员的生理功能和结构特征，以及它们作为内源性诱变剂在致癌过程中导致超突变的作用。我们还回顾了 APOBEC-CRISPR/Cas9 基因编辑工具的各种迭代，指出了它们的特点和局限性以及未来发展的可能性。
