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Tunability of DNA polymerase stability during eukaryotic DNA replication

Journal Article


Abstract


  • Summary

    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 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.

Publication Date


  • 2019

Citation


  • Lewis, J., Spenkelink, L., Schauer, G., Yurieva, O., Mueller, S., Natarajan, V., . . . van Oijen, A. (2019). Tunability of DNA polymerase stability during eukaryotic DNA replication. doi:10.1101/602086

Web Of Science Accession Number


Abstract


  • Summary

    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 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.

Publication Date


  • 2019

Citation


  • Lewis, J., Spenkelink, L., Schauer, G., Yurieva, O., Mueller, S., Natarajan, V., . . . van Oijen, A. (2019). Tunability of DNA polymerase stability during eukaryotic DNA replication. doi:10.1101/602086

Web Of Science Accession Number