Single-molecule studies of repair proteins in base excision repair

Abstract

Base excision repair (BER) is an essential cellular mechanismthat repairs small, non-helix-distorting base lesions in DNA,resulting from oxidative damage, alkylation, deamination, orhydrolysis. This review highlights recent advances in understandingthe molecular mechanisms of BER enzymes throughsingle-molecule studies. We discuss the roles of DNA glycosylasesin lesion recognition and excision, with a focus onfacilitated diffusion mechanisms such as sliding and hoppingthat enable efficient genome scanning. The dynamics of apurinic/apyrimidinic endonucleases, especially the coordination betweenAPE1 and DNA polymerase  (Pol ), are explored todemonstrate their crucial roles in processing abasic sites. Thereview further explores the short-patch and long-patch BERpathways, emphasizing the activities of Pol , XRCC1, PARP1,FEN1, and PCNA in supporting repair synthesis and ligation. Additionally, we highlight the emerging role of UV-DDB as ageneral damage sensor in BER, extending its recognized functionbeyond nucleotide excision repair. Single-molecule techniqueshave been instrumental in uncovering the complex interactionsand mechanisms of BER proteins, offering unprecedented insightsthat could guide future therapeutic strategies for maintaininggenomic stability.