![]() ![]() We show that Dna2 associates with the replisome protein And-1 in a cell cycle-dependent manner. Here we investigated the role hDna2 plays in DNA replication. We previously demonstrated that the human Dna2 orthologue (hDna2) localizes to the nucleus and contributes to genomic stability. These findings suggest that the genomic instability observed in hDna2-depleted cells does not arise from defective OF maturation and that hDna2 plays a role in DNA replication that is distinct from FEN1 and OF maturation.ĪB - Dna2 is an essential helicase/nuclease that is postulated to cleave long DNA flaps that escape FEN1 activity during Okazaki fragment (OF) maturation in yeast. In contrast, we found that FEN1 expression in hDna2-depleted cells failed to rescue genomic instability. Prior work in yeast demonstrated that ectopic expression of FEN1 rescues Dna2 defects. Analysis of hDna2-depleted cells failed to reveal a defect in OF maturation or replication fork progression. Strikingly, the reduction in OF maturation had no impact on replication fork progression, indicating that fork movement is not tightly coupled to lagging strand maturation. As expected, FEN1 depletion led to a significant reduction in OF maturation. We next examined the impact of hDna2 on OF maturation and replication fork progression in human cells. In addition, we observed reduced origin firing in hDna2-depleted cells consistent with Chk1 activation. Depletion of hDna2 resulted in S/G(2) phase-specific DNA damage as evidenced by increased γ-H2AX, replication protein A foci, and Chk1 kinase phosphorylation, a readout for activation of the ATR-mediated S phase checkpoint. N2 - Dna2 is an essential helicase/nuclease that is postulated to cleave long DNA flaps that escape FEN1 activity during Okazaki fragment (OF) maturation in yeast. T1 - Okazaki fragment processing-independent role for human Dna2 enzyme during DNA replication These findings suggest that the genomic instability observed in hDna2-depleted cells does not arise from defective OF maturation and that hDna2 plays a role in DNA replication that is distinct from FEN1 and OF maturation.", ![]() ![]() Abstract = "Dna2 is an essential helicase/nuclease that is postulated to cleave long DNA flaps that escape FEN1 activity during Okazaki fragment (OF) maturation in yeast. ![]()
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