Multiple roles for Mcm10 during lagging strand synthesis

Abstract

In lagging strand synthesis, Okazaki fragments are initiated by DNA polymerase‐alpha/primase, which produces a short RNA/DNA primer. Subsequently, a switch occurs from pol‐alpha to pol‐delta. We believe that minichromosome maintenance protein (Mcm) 10 coordinates this switch as it interacts with pol‐alpha and proliferating cell nuclear antigen (PCNA), the accessory factor for pol‐delta. This polymerase switch may be triggered by the non‐proteolytic ubiquitination of Mcm10, which is a pre‐requisite for Mcm10 to bind PCNA. Importantly, ubiquitinated Mcm10 can no longer interact with pol‐alpha. Because we have shown that the catalytic subunit of pol‐alpha is rapidly degraded in the absence of Mcm10, this modification might provide a mechanism to release pol‐alpha from the replication fork. We are currently trying to understand how Mcm10 is ubiquitinated and whether the Mcm10‐regulated degradation of pol‐alpha plays a role during replication.