DNA ligase 1 (LIG1) is a critical enzyme that seals nicks in double-stranded DNA during DNA replication and repair processes 1. LIG1 plays an essential role in Okazaki fragment processing during lagging strand DNA synthesis, where it ligates 5'-phosphorylated nicks between DNA fragments 2. The enzyme is specifically involved in base excision repair, mismatch repair, and nucleotide excision repair pathways as part of multiprotein complexes 3. LIG1 functions together with other DNA repair proteins including POLD1 and XRCC1, and its activity can be regulated through transcriptional mechanisms involving transcription factors like FOXA1 and TET1 3. Clinically, LIG1 deficiency is associated with increased chr19 instability and poor prognosis across multiple cancer types 4. Hemizygous loss or reduced expression of LIG1 correlates with chemotherapy resistance, particularly carboplatin resistance in triple-negative breast cancer, and contributes to therapeutic resistance through enhanced DNA repair capacity 4. Additionally, LIG1 deficiency creates synthetic lethality with PARP inhibitors, making it a potential biomarker for stratifying cancer patients for targeted therapy 5.