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Enhanced Sensitivity of Neil1-/- Mice to Chronic UVB Exposure

Published

Author(s)

Pawel Jaruga, M Miral Dizdar, Marcus J. Calkins, Vladimir Vartanian, Amanda McCullough, R. S. Lloyd, Guldal Kirkali

Abstract

Oxidative stress and oxidatively induced DNA base damage are central mediators of UV-induced carcinogenesis and skin aging. However, increased steady-state levels of oxidatively induced DNA base damage have not been reported after chronic UV exposure. Accumulation of oxidatively induced DNA base damage is governed by rates of lesion formation and repair in which repair is performed by the DNA base excision repair (BER) pathway. DNA glycosylases, such as 8-oxoguanine glycosylase (OGG1) and Nei-Endonuclease VIII-Like 1 (NEIL1) initiate BER. In the current study, UV light (UVB) was used to elicit protracted low-level of reactive oxygen species (ROS) challenge in wild-type (WT) and Neil1-/- mouse skin. Relative to WT controls, Neil1-/- mice showed an increased sensitivity to tissue destruction from chronic UVB exposure. Levels of several oxidatively induced DNA lesions were measured including 4,6-diamino-5-formamidopyrimidine (FapyGua), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyAde), 8-hydroxyguanine (8-OH-Gua), 5,6-dihydroxyuracil (5,6-diOH-Ura) and thymine glycol (ThyGly). In WT mice, chronic UVB exposure led to increased steady-state levels of FapyGua, FapyAde, and ThyGly, with no significant increases in 8-OH-Gua or 5,6-diOH-Ura. Interestingly, the DNA lesions that accumulated were all substrates of NEIL1. Collectively, these data suggest that NEIL1-initiated repair of a subset of oxidatively induced DNA base lesions may be insufficient during chronic UV exposure in mouse skin.
Citation
Dna Repair

Keywords

oxidatively induced DNA base damage, UV exposure, NEIL1, OGG1

Citation

Jaruga, P. , , M. , Calkins, M. , Vartanian, V. , McCullough, A. , Lloyd, R. and Kirkali, G. (2016), Enhanced Sensitivity of Neil1-/- Mice to Chronic UVB Exposure, Dna Repair, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=919055 (Accessed April 24, 2024)
Created October 28, 2016, Updated March 22, 2017