A short review on the implications of base excision repair pathway for neurons: relevance to neurodegenerative diseases.
Oxidative DNA damage results from the attack by reactive oxygen and nitrogen species (ROS/RNS) on human genome. This includes base modifications such as oxidized bases, abasic (AP) sites, and single-strand breaks (SSBs), all of which are repaired by the base excision repair (BER) pathway, one among the six known repair pathways. BER-pathway in mammalian cells involves several evolutionarily conserved proteins and is also linked to genome replication and transcription. The BER-pathway enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease (APE1), form complexes with downstream repair enzymes via protein-protein and DNA-protein interactions. An emerging concept for BER proteins is their involvement in non-canonical functions associated to RNA metabolism, which is opening new interesting perspectives. Various mechanisms that are underlined in maintaining neuronal cell genome integrity are identified, but are inconclusive in providing protection against oxidative damage in neurodegenerative disorders, main emphasis is given towards the role played by the proteins of BER-pathway that is discussed. In addition, mechanisms of action of BER-pathway in nuclear vs. mitochondria as well as the non-canonical functions are discussed in connection to human neurodegenerative diseases.
Center for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, Punjab, India; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: anilmantha@gmail.com.
Anil K
AK
Mantha
Center for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151 001, Punjab, India.
Bibekananda
B
Sarkar
Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy.
Gianluca
G
Tell
D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D011485:Protein Binding; D055503:Protein Multimerization; D026361:Reactive Nitrogen Species / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000633:toxicity
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D004247:DNA; D045643:DNA Repair Enzymes
AP endonuclease 1; Base excision repair; DNA glycosylase; Neurodegenerative disorders; Oxidative stress; Single-strand break repair