Primer handoff between DNA primase and DNA polymerase α

Abstract

DNA replication is a fundamental process. In eukaryotes, the first step in daughter strand synthesis is the generation of a short (~10 nt) RNA primer by DNA primase, followed by transfer of the primer to DNA polymerase α (Pol α) for extension by ~20 nts (O'Brien et al., 2017; Burgers & Kunkel, 2017; Pellegrini, 2012; O'Brien et al., 2018; O'Brien, Holt, Salay, Chazin, & Barton, 2018). Although the catalytic activity and structures of primase and Pol a have been extensively studied (Burgers & Kunkel, 2017; Pellegrini, 2012; O'Brien et al., 2018; O'Brien, Holt, Salay, Chazin, & Barton, 2018), the molecular mechanism of primer handoff between primase and Pol α remains largely unknown. We have proposed that redox switching of the [4Fe4S] cluster in primase is important for primer truncation and handoff to Pol a (O'Brien et al., 2017; O'Brien et al., 2018). Eukaryotic Pol α is composed of a catalytic subunit (p180) and a regulatory subunit (p68). The p180 subunit contains a [4Fe4S] cluster.

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