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裸鼹鼠细胞比小鼠细胞表现出更高效的切除修复能力。

Naked mole rat cells display more efficient excision repair than mouse cells.

作者信息

Evdokimov Alexei, Kutuzov Mikhail, Petruseva Irina, Lukjanchikova Natalia, Kashina Elena, Kolova Ekaterina, Zemerova Tatyana, Romanenko Svetlana, Perelman Polina, Prokopov Dmitry, Seluanov Andrei, Gorbunova Vera, Graphodatsky Alexander, Trifonov Vladimir, Khodyreva Svetlana, Lavrik Olga

机构信息

Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia.

Institute of Cytology and Genetics, Novosibirsk 630090, Russia.

出版信息

Aging (Albany NY). 2018 Jun 20;10(6):1454-1473. doi: 10.18632/aging.101482.

Abstract

Naked mole rat (NMR) is the long-lived and tumor-resistant rodent. NMRs possess multiple adaptations that may contribute to longevity and cancer-resistance. However, whether NMRs have more efficient DNA repair have not been directly tested. Here we compared base excision repair (BER) and nucleotide excision repair (NER) systems in extracts from NMR and mouse fibroblasts after UVC irradiation. Transcript levels of the key repair enzymes demonstrated in most cases higher inducibility in the mouse vs the NMR cells. Ratios of repair enzymes activities in the extracts somewhat varied depending on post-irradiation time. NMR cell extracts were 2-3-fold more efficient at removing the bulky lesions, 1.5-3-fold more efficient at removing uracil, and about 1.4-fold more efficient at cleaving the AP-site than the mouse cells, while DNA polymerase activities being as a whole higher in the mouse demonstrate different patterns of product distribution. The level of poly(ADP-ribose) synthesis was 1.4-1.8-fold higher in the NMR cells. Furthermore, NMR cell extracts displayed higher binding of PARP1 to DNA probes containing apurinic/apyrimidinic site or photo-reactive DNA lesions. Cumulatively, our results suggest that the NMR has more efficient excision repair systems than the mouse, which may contribute to longevity and cancer resistance of this species.

摘要

裸鼹鼠是一种寿命长且具有抗瘤能力的啮齿动物。裸鼹鼠具有多种适应性特征,可能有助于其长寿和抗癌。然而,裸鼹鼠是否具有更高效的DNA修复能力尚未得到直接验证。在此,我们比较了紫外线C(UVC)照射后裸鼹鼠和小鼠成纤维细胞提取物中的碱基切除修复(BER)和核苷酸切除修复(NER)系统。在大多数情况下,关键修复酶的转录水平在小鼠细胞中比在裸鼹鼠细胞中具有更高的诱导性。提取物中修复酶活性的比例在一定程度上因照射后的时间而异。与小鼠细胞相比,裸鼹鼠细胞提取物在去除大分子损伤方面效率高2至3倍,在去除尿嘧啶方面效率高1.5至3倍,在切割无嘌呤/无嘧啶位点方面效率高约1.4倍,而小鼠细胞中DNA聚合酶的整体活性较高,呈现出不同的产物分布模式。裸鼹鼠细胞中聚(ADP - 核糖)合成水平高1.4至1.8倍。此外,裸鼹鼠细胞提取物对含有无嘌呤/无嘧啶位点或光反应性DNA损伤的DNA探针表现出更高的PARP1结合能力。综合来看,我们的结果表明,裸鼹鼠比小鼠具有更高效的切除修复系统,这可能有助于该物种的长寿和抗癌能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c38/6046242/77f6b11ff326/aging-10-101482-g001.jpg

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