Human DNA polymerase λ functionally and physically interacts with proliferating cell nuclear antigen in normal and translesion DNA synthesis

Proliferating cell nuclear antigen (PCNA) has been shown to interact with a variety of DNA polymerases (pol) such as pol δ, pol ε, pol τ, pol κ, pol η, and pol β. Here we show that PCNA directly interacts with the newly discovered pol λ cloned from human cells. This interaction stabilizes the binding of pol λ to the primer template, thus increasing its affinity for the hydroxyl primer and its processivity in DNA synthesis. However, no effect of PCNA was detected on the rate of nucleotide incorporation or discrimination efficiency by pol λ. PCNA was found to stimulate efficient synthesis by pol λ across an abasic (AP) site. When compared with pol δ, human pol λ showed the ability to incorporate a nucleotide in front of the lesion. Addition of PCNA led to efficient elongation past the AP site by pol λ but not by pol δ. However, when tested on a template containing a bulky DNA lesion, such as the major cisplatin Pt-d(GpG) adduct, PCNA could not allow translesion synthesis by pol λ. Our results suggest that the complex between PCNA and pol λ may play an important role in the bypass of abasic sites in human cells.