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

SIMPLE SUMMARY: Under the continuous stimulation of oxidizing substances, DNA bases undergo oxidative damage and excision repair alternately at all times. Once this process becomes abnormal, many pathological diseases will appear one after another. NEIL3 is an important DNA glycosylase in the base excision repair pathway and is involved in oxidative DNA base damage repair. In recent years, several studies have confirmed that abnormal expression of NEIL3 is closely associated with cancers and cardiovascular and neurological diseases, and it may be a potential prognostic molecule and therapeutic target. circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we not only describe the structural specificity and functional specificity of NEIL3, but also focus on NEIL3 and circNEIL3 in cancer progression and prognosis. In addition, we also discuss the link between NEIL3 and the progression of cardiovascular and neurological diseases. 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.