Abstract

Three DNA polymerases of the B family function at the replication fork in eukaryotic cells: DNA polymerases α, δ, and ε. DNA polymerase α, an heterotetramer composed of two primase subunits and two polymerase subunits, initiates replication. DNA polymerases δ and ε elongate the primers generated by pol α. The DNA polymerase from bacteriophage RB69 has served as a model for eukaryotic B family polymerases for some time. The recent crystal structures of pol δ, α, and ε revealed similarities but also a number of unexpected differences between the eukaryotic polymerases and their bacteriophage counterpart, and also among the three yeast polymerases. This review will focus on their shared structural elements as well as the features that are unique to each of these polymerases.

Highlights

  • Replication in the nucleus of eukaryotic cells employs three DNA polymerases: polymerase α, δ, and ε (Hubscher et al, 2002; Pavlov et al, 2006b; Kunkel and Burgers, 2008; Loeb and Monnat, 2008; Burgers, 2009; Pavlov and Shcherbakova, 2010; Lange et al, 2011)

  • The primase subunits initiate DNA replication by synthesizing short (7–12 ribonucleotides) RNA primers, which are extended by polymerase α (Pellegrini, 2012)

  • A DIFFERENT PROTEIN FOLD IN THE INACTIVATED EXONUCLEASE SUBDOMAIN The proofreading activity is abolished in pol α, due to mutations in all four carboxylates (Asp114/Glu116/Asp222/Asp327 in RB69 gp43 correspond to Ser542/Gln544/Tyr644/Asn757 in a structure-based alignment) (Table 2)

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Summary

Introduction

Replication in the nucleus of eukaryotic cells employs three DNA polymerases: polymerase α, δ, and ε (Hubscher et al, 2002; Pavlov et al, 2006b; Kunkel and Burgers, 2008; Loeb and Monnat, 2008; Burgers, 2009; Pavlov and Shcherbakova, 2010; Lange et al, 2011). A DIFFERENT PROTEIN FOLD IN THE INACTIVATED EXONUCLEASE SUBDOMAIN The proofreading activity is abolished in pol α, due to mutations in all four carboxylates (Asp114/Glu116/Asp222/Asp327 in RB69 gp43 correspond to Ser542/Gln544/Tyr644/Asn757 in a structure-based alignment) (Table 2).

Results
Conclusion

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