DNA ligase 1 (LIG1) (LIG1)

DNA ligase 1 (LIG1) is a critical enzyme involved in maintaining genomic integrity by sealing nicks in the phosphodiester backbone of DNA. It plays a central role in DNA replication, specifically in the joining of Okazaki fragments on the lagging strand, as well as in various DNA repair pathways such as base excision repair (BER) and long-patch nucleotide excision repair (UniProt P18858). In the context of oncology, LIG1 is frequently overexpressed in rapidly dividing cancer cells to support accelerated DNA synthesis (PubMed 1563284). Fludarabine, a purine nucleoside analog, is metabolized into its active triphosphate form (F-ara-ATP), which has been shown to inhibit LIG1 activity (PubMed 1563284). This inhibition prevents the ligation of DNA strands, resulting in the accumulation of single-strand breaks, stalled replication forks, and ultimately, the induction of apoptosis in malignant cells (PubChem CID 30751). LIG1 is therefore a significant target for nucleoside analogs used in chemotherapy, and its expression levels may serve as a biomarker for treatment response.

Other names

DNA ligase IPolydeoxyribonucleotide synthase [ATP] 1LIG1

Fludarabine triphosphate (F-ara-ATP) acts as a competitive inhibitor of DNA ligase 1, preventing the sealing of DNA nicks and leading to the accumulation of DNA strand breaks and apoptosis.