Okazaki fragment maturation Sample Clauses

Okazaki fragment maturation. Following establishment of an active CMG, synthesis proceeds bi-directionally from origins of replication. Given the intrinsic directionality of the CMG, the template is unwound and read in a 3’ to 5’ direction along the DNA. The nascent strands are then elongated by DNA polymerases that incorporate dNTPs in the 5’ to 3’ direction along the DNA. This means that one strand can be synthesised continuously (leading strand) whereas the other must be synthesised discontinuously and in the opposite direction (lagging strand). The DNA polymerase α/primase complex synthesises and elongates short RNA primers (~20 nucleotides in total) that are extended on the leading strand primarily by DNA polymerase ε and on the lagging strand by DNA polymerase δ (Xxxxxxx et al. 2015; Xxxxxxxxx et al. 2015; Xxxxxxx and Xxxxxx, 2017). Recently, it was suggested that DNA polymerase δ also plays a role in the establishment of leading strand synthesis (Xxxxxx et al. 2017). Unlike the leading strand, replication on the lagging strand is achieved through the synthesis of short fragments, which are eventually processed (matured) to form a single, continuous strand of DNA. These are called Okazaki fragments in honour of Xxxx and Xxxxxx Xxxxxxx, who first proposed a model for their synthesis in 1968 (Xxxxxxx et al. 1968). Roughly 50 million Okazaki fragments are synthesised during a single S-phase in mammalian cells, underlying the need for rapid yet accurate maturation (Xxxxxxxxxxxx and Xxxxxxx, 2011). In addition, DNA polymerase α/primase lacks 3’-5’ exonuclease (‘proofreading’) activity and is thus considered to be an error-prone polymerase (Xxxxxxxxxxxx and Xxxxxxx, 2013). It is therefore important that the RNA primer and any DNA synthesised by DNA polymerase α/primase is removed and replaced by a high fidelity polymerase, such as DNA polymerase δ or DNA polymerase ε (Xxxxxxxxxxxx and Xxxxxxx, 2013).