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

Naked mole rat cells display more efficient excision repair than mouse cells.
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DOI:
10.18632/aging.101482
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发表时间:
2018-06-20
期刊:
Aging
影响因子:
--
通讯作者:
Lavrik O
Lavrik O
中科院分区:
其他
文献类型:
--
作者:
Evdokimov A;Kutuzov M;Petruseva I;Lukjanchikova N;Kashina E;Kolova E;Zemerova T;Romanenko S;Perelman P;Prokopov D;Seluanov A;Gorbunova V;Graphodatsky A;Trifonov V;Khodyreva S;Lavrik O

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裸鼹鼠(NMR)是一种长寿、抗肿瘤的啮齿类动物。核磁共振具有多种适应性,可能有助于长寿和抗癌。然而,核磁共振是否有更有效的DNA修复还没有直接测试。在这里,我们比较了紫外线照射后核磁共振和小鼠成纤维细胞提取物的碱基切除修复(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中比在核磁共振细胞中表现出更高的诱导性。修复酶活性的比例随辐照后时间的不同而有所不同。核磁共振细胞提取物去除大肿块的效率是小鼠细胞的2 - 3倍,去除尿嘧啶的效率是1.5 - 3倍,切割ap位点的效率是1.4倍,而DNA聚合酶活性在小鼠中整体较高,表现出不同的产物分布模式。在核磁共振细胞中,聚腺苷核糖(adp -核糖)的合成水平高出1.4 - 1.8倍。此外,核磁共振细胞提取物显示PARP1与含有无尿嘧啶/无嘧啶位点或光反应性DNA病变的DNA探针的结合更高。总的来说,我们的研究结果表明,核磁共振比小鼠具有更有效的切除修复系统,这可能有助于该物种的寿命和抗癌能力。
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.
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