Preliminary study on the function of the POLD1 (CDC2) EXON2 c.56G>A mutation

BACKGROUND: Fanconi anemia (FA) is a rare recessive disease characterized by DNA damage repair deficiency, and DNA polymerase δ (whose catalytic subunit is encoded by POLD1, also known as CDC2) is closely related to DNA damage repair. Our previous study identified a novel POLD1 missense mutation c.56G>A (p. Arg19>His) in FA family members. However, the function of the POLD1 missense mutation is currently unknown. This study aimed to uncover the biological function of the POLD1 missense mutation. METHODS: Stable cell lines overexpressing wild‐type POLD1 or mutant POLD1 (c.56G>A, p.Arg19His) were constructed by lentivirus infection. Cell growth curve analysis, cell cycle analysis, and a comet assay were used to analyze the function of the POLD1 mutation. RESULTS: The growth and proliferative ability of the cells with POLD1 mutation was decreased significantly compared with those of the wild‐type cells (Student's t test, p < .05). The percentage of cells in the G0/G1 phase increased, and the percentage of cells in the S phase decreased significantly when POLD1 was mutated (Student's t test, p < .05). Moreover, the Olive tail moment value of the cells with the POLD1 mutation was significantly higher than that of the cells with wild‐type POLD1 after H(2)O(2) treatment. CONCLUSIONS: The POLD1 mutation inhibited cell proliferation, slowed cell cycle progression, and reduced DNA damage repair.