The present study identifies Mcm10 as the factor that enables CMG to rapidly bypass a block on the lagging strand. Mcm10 is unique to eukaryotes and is an essential gene product that, when mutated, causes abortive entry into S-phase (Du et al., 2012; Merchant et al., 1997; Solomon et al., 1992; Thu and Bielinsky, 2013). Mcm10 has two internal DNA binding sites (Du et al., 2012; Robertson et al., 2008; Warren et al., 2008) and is known to bind Mcm2-7 and Cdc45 (Christensen and Tye, 2003; Di Perna et al., 2013; Douglas and Diffley, 2016; Perez-Arnaiz et al., 2016). Mcm10 is generally thought to act as an initiation factor (Thu and Bielinsky, 2013). The licencing of an origin in G1 phase involves several proteins to form a head-to-head double hexamer of Mcm2-7. Additional initiation factors transform the Mcm2-7 double hexamer into two head-to-head CMGs during S phase (Bell and Labib, 2016) but Mcm10 is not required for this action (Kanke et al., 2012; van Deursen et al., 2012; Watase et al., 2012; Yeeles et al., 2015). Mcm10 is only required at the last step of initiation and is proposed to either activate CMG helicase or help separate the two CMGs for bidirectional replication forks (Kanke et al., 2012; Lõoke et al., 2017; Quan et al., 2015; van Deursen et al., 2012; Watase et al., 2012; Yeeles et al., 2015). Additional studies indicate that Mcm10 may also function at replication forks (Chadha et al., 2016; Gambus et al., 2006; Lõoke et al., 2017; Ricke and Bielinsky, 2004).