Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1

DNA ligase I (LigI), the predominant enzyme that joins Okazaki fragments, interacts with PCNA and Pol delta. LigI also interacts with UHRF1, linking Okazaki fragment joining with DNA maintenance methylation. Okazaki fragments can also be joined by a relatively poorly characterized DNA ligase III -dependent backup pathway. In this study, we used CH12F3 cells to examine the effect of LigI-deficiency on gene expression as well as proteins at the replication fork. As human LIG1 deficiency syndromes have been described, and LigI is a promising target in ovarian cancer, the mechanisms of lagging-strand DNA synthesis and associated DNA methylation and histone deposition dynamics in LigI deficient cells are relevant to understanding disease pathogenesis and the potential utility of LigI inhibition for treating cancer.