A recombinant fungal photolyase autonomously enters human cell nuclei to fix UV-induced DNA lesions.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology Letters Pub Date : 2024-06-01 Epub Date: 2024-03-25 DOI:10.1007/s10529-024-03474-3

Yuting Bao, Weiguo Fang

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Abstract

Solar ultraviolet radiations induced DNA damages in human skin cells with cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts (6-4PPs) as the most frequent lesions. CPDs are repaired much slower than 6-4PPs by the nucleotide excision repair pathway, which are thus the major lesions that interfere with key cellular processes and give rise to gene mutations, possibly resulting in skin cancer. In prokaryotes and multicellular eukaryotes other than placental mammals, CPDs can be rapidly repaired by CPD photolyases in one simple enzymatic reaction using the energy of blue light. In this study, we aim to construct recombinant CPD photolyases that can autonomously enter human cell nuclei to fix UV-induced CPDs. A fly cell penetration peptide and a viral nucleus localization signal peptide were recombined with a fungal CPD photolyase to construct a recombinant protein. This engineered CPD photolyase autonomously crosses cytoplasm and nuclear membrane of human cell nuclei, which then efficiently photo-repairs UV-induced CPD lesions in the genomic DNA. This further protects the cells by increasing SOD activity, and decreasing cellular ROSs, malondialdehyde and apoptosis.

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重组真菌光解酶可自主进入人类细胞核，修复紫外线诱导的 DNA 损伤。

太阳紫外线辐射会诱导人类皮肤细胞的 DNA 损伤，其中环丁烷嘧啶二聚体（CPD）和（6-4）光产物（6-4PPs）是最常见的损伤。环丁烷嘧啶二聚体在核苷酸切除修复途径中的修复速度比 6-4PPs 慢得多，因此是干扰关键细胞过程和导致基因突变的主要病变，可能导致皮肤癌。在原核生物和除胎盘哺乳动物以外的多细胞真核生物中，CPD 可通过 CPD 光解酶利用蓝光的能量在一个简单的酶促反应中快速修复。在本研究中，我们旨在构建重组 CPD 光解酶，使其能自主进入人细胞核修复紫外线诱导的 CPD。我们将苍蝇细胞穿透肽和病毒细胞核定位信号肽与真菌 CPD 光解酶重组，构建了一种重组蛋白。这种经过改造的 CPD 光解酶能自主穿过人细胞核的细胞质和核膜，然后对基因组 DNA 中紫外线诱导的 CPD 病变进行有效的光修复。它还能提高 SOD 活性，减少细胞内的 ROS、丙二醛和细胞凋亡，从而进一步保护细胞。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.