Detection and Sequencing of Okazaki Fragments in S. cerevisiae

Methods Mol Biol. 2015:1300:141-53. doi: 10.1007/978-1-4939-2596-4_10.

Abstract

We have previously demonstrated that lagging-strand synthesis in budding yeast is coupled with chromatin assembly on newly synthesized DNA. Using a strain of S. cerevisiae in which DNA ligase I can be conditionally depleted, we can enrich and purify Okazaki fragments. We delineate a method to extract, end label, and visualize Okazaki fragments using denaturing agarose gel electrophoresis. Furthermore, we describe an ion-exchange chromatographic method for purification of fragments and preparation of strand-specific sequencing libraries. Deep sequencing of Okazaki fragments generates a comprehensive, genomic map of DNA synthesis, starting from a single asynchronous culture. Altogether this approach represents a tractable system to investigate key aspects of DNA replication and chromatin assembly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA / genetics*
  • DNA, Fungal / metabolism
  • Electrophoresis, Agar Gel
  • Genome, Fungal
  • Saccharomyces cerevisiae / genetics*
  • Sequence Analysis, DNA / methods*
  • Staining and Labeling

Substances

  • DNA, Fungal
  • Okazaki fragments
  • DNA