Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer

Abstract

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Inhibition of TRPM3 by primidone provides a potential therapeutic method for adenomyosis management

“…Finally, based on the fold changes in expression in RNA-Seq and prospective therapeutic value, we veri ed the expression ratios of CHIL1, COL9A2, PSMC3IP, NEIL3, and SPC24. These genes play an important role in multiple pathological mechanisms, including in ammation, tissue remodeling, injury, DNA repair and cell mitosis [33][34][35], which deserves further investigation. In addition, decreased PSMC3IP and SPC24 have also been reported to contribute to female infertility via meiotic failure [36,37], which might be further studied in the eld of adenomyosis-related reproductive issues.…”

Identification and validation of Nei-like DNA glycosylase 2 as a novel prognostic biomarker in cervical cancer

“…Endogenous or exogenous factors such as in ammation, oxidative stress, ionizing radiation, and metabolites can promote the production of reactive oxygen species or reactive oxygen and nitrogen species, whose accumulation can lead to oxidative damage. DNA damage, if not quickly repaired, may cause base mismatches, hinder DNA replication or transcription, or destroy the stability and integrity of the genome, eventually promoting aging and cancer (Chen et al, 2022). Base excision repair (BER) is the main repair method for most oxidative DNA base lesions.…”