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.
Highlights
Aging and cancer are accompanied by the accumulation of mutations in the genome, genomic instability and dysregulation of transcription patterns [1]
To characterize the response of DNA repair systems to exposure to UVC irradiation, we analyzed the functionality of the base excision repair (BER) and nucleotide excision repair (NER) systems in Naked mole rat (NMR) and mouse fibroblasts using several approaches and tested cell proliferation after UVC irradiation
Analysis of metabolic activity/viability of cells at the time points after irradiation that were used for the tests of enzymatic activities and evaluation of mRNA levels (Fig. 1S) revealed neither significant variations of the metabolic activity nor the difference between NMR and mouse cells; this indirectly testifies to comparable sensitivity of the cells to UVC-irradiation
Summary
Aging and cancer are accompanied by the accumulation of mutations in the genome, genomic instability and dysregulation of transcription patterns [1]. NMRs may have more efficient BER and NER systems that protect the cells from mutations coupled with heightened stress responses. One of the immediate cellular responses to DNA damage is poly(ADP-ribosyl)ation, i.e., the transi-ent covalent modification of proteins by a homo-polymer consisting of ADP ribose units. This reaction is catalyzed by poly(ADP-ribose)polymerases (PARPs), which are activated by DNA damage. PARPs and their activity are thought to act as an essential system for regulation of several DNA repair systems including BER and NER [21,22,23,24]. Our results suggest that NMR has more efficient BER and NER systems than the short-lived and tumor-prone mouse
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
