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

Published

December 1, 2016

Author(s)

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

Abstract

DNA base damage induced by oxidative stress and reactive oxygen species (ROS) are thought to be central mediators of ultraviolet light (UV)-induced carcinogenesis and skin aging. However, increased steady-state levels of ROS-induced DNA base damage have not been reported after chronic UV exposure. Accumulation of ROS-induced DNA base damage is governed by rates of lesion formation and repair. Repair is generally performed by the Base Excision Repair (BER) pathway, which is initiated by DNA glycosylases, such as 8-oxoguanine glycosylase and Nei-Endonuclease VIII-Like 1 (NEIL1). In the current study, UV light (UVB) was used to elicit protracted low- level ROS challenge in wild-type (WT) and Neil1-/- mouse skin. Relative to WT controls, Neil1-/- mice showed an increased sensitivity to tissue destruction from the chronic UVB exposure. Levels of several ROS-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 known substrates of NEIL1. Collectively, these data suggest that NEIL1-initiated repair of a subset of ROS-induced DNA base lesions may be insufficient during chronic UV exposure in mouse skin.

Citation

Dna Repair

Volume

48

Pub Type

Journals

Download Paper

DOI Link

Keywords

UVB, Neil1, skin damage, oxidatively induced DNA lesions

Citation

, M. , Calkins, M. , Vartanian, V. , Kirkali, G. , McCullough, A. , Lloyd, R. and Jaruga, P. (2016), Enhanced Sensitivity of Neil1-/- Mice to Chronic UVB Exposure, Dna Repair, [online], https://doi.org/10.1016/j.dnarep.2016.10.010 (Accessed December 13, 2024)