Tunability of DNA Polymerase Stability during Eukaryotic DNA Replication

Authors

Jacob S. LewisFollow
Lisanne Maria Spenkelink, University of WollongongFollow
Grant Schauer
Olga Yurieva
Stefan Mueller, University of WollongongFollow
Varsha Natarajan, University of WollongongFollow
Gurleen Kaur, University of WollongongFollow
Claire Maher, University of Wollongong
Callum Kay, University of Wollongong
Michael O'Donnell
Antoine M. van Oijen, University of WollongongFollow

RIS ID

140728

Publication Details

Lewis, J., Spenkelink, L., Schauer, G., Yurieva, O., Mueller, S., Natarajan, V., Kaur, G., Maher, C., Kay, C., O'Donnell, M. & van Oijen, A. (2020). Tunability of DNA Polymerase Stability during Eukaryotic DNA Replication. Molecular Cell, 77 (1), 17-25.

Abstract

2019 Elsevier Inc. Structural and biochemical studies have revealed the basic principles of how the replisome duplicates genomic DNA, but little is known about its dynamics during DNA replication. We reconstitute the 34 proteins needed to form the S. cerevisiae replisome and show how changing local concentrations of the key DNA polymerases tunes the ability of the complex to efficiently recycle these proteins or to dynamically exchange them. Particularly, we demonstrate redundancy of the Pol α-primase DNA polymerase activity in replication and show that Pol α-primase and the lagging-strand Pol δ can be re-used within the replisome to support the synthesis of large numbers of Okazaki fragments. This unexpected malleability of the replisome might allow it to deal with barriers and resource challenges during replication of large genomes.