Research Paper Volume 10, Issue 6 pp 1454—1473
Naked mole rat cells display more efficient excision repair than mouse cells
- 1 Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, Russia
- 2 Institute of Molecular and Cellular Biology, Novosibirsk 630090, Russia
- 3 Institute of Cytology and Genetics, Novosibirsk 630090, Russia
- 4 Department of Biology, University of Rochester, Rochester, NY 14627, USA
- 5 Equal contribution
Received: February 20, 2018 Accepted: June 13, 2018 Published: June 20, 2018
https://doi.org/10.18632/aging.101482How to Cite
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.
Abbreviations
AP site: apurinic/apyrimidinic site; APE1: apurinic/ apyrimidinic endonuclease 1; Polβ: DNA polymerase β; dCFAP: exo-N-[2-[N-(4-azido-2,5-difluoro-3-chloro-pyridin-6-yl)-3-aminopropionyl]aminoethyl]-2'-deoxy-cytidine; NMR: naked mole rat (Heterocephalus glaber); PAR: polymer of ADP-ribose; PARylation: poly(ADP-ribosyl)ation.