Structural Study of the Complex Between DNA Polymerase Iota and Ub-PCNA
Abstract
DNA polymerase iota (polι) is a member of the Y-family, polymerases which are key components in translesion synthesis (TLS). As part of the DNA damage response, TLS allows cells to bypass damaged template DNA. Each member of the Y-family is capable of accurately replicating across from certain lesions. All Y-family polymerases are recruited by ubiquitination of the DNA sliding clamp, PCNA, by direct interaction with PCNA and ubiquitin. The mechanism of polymerase choice is not well understood, nor are the interactions between Ub-PCNA and the TLS polymerases. We studied the structure of the complex between the interacting region of polι and Ub-PCNA. Polι appears to be unable to bind all three monomers of homotrimeric Ub-PCNA simultaneously, even in a heavily truncated form. The maximum complex ratio observed was two polymerases per Ub-PCNA ring. This assembly ratio limit may give insight into switching of multiple polymerases at the PCNA platform in DNA damage response.