How the cell deals with DNA nicks

Parie Garg, Peter M.J. Burgers

Research output: Contribution to journalShort surveypeer-review

16 Scopus citations

Abstract

During lagging strand DNA replication, the Okazaki fragment maturation machinery is required to degrade the initiator RNA with high speed and efficiency, and to generate with great accuracy a proper DNA nick for closure by DNA ligase. Several operational parameters are important in generating and maintaining a ligatable nick. These are the strand opening capacity of the lagging strand DNA polymerase δ (Pol δ), and its ability to limit strand opening to that of a few nucleotides. In the presence of the flap endonuclease FEN1, Pol δ rapidly hands off the strand-opened product for cutting by FEN1, while in its absence, the ability of DNA polymerase δ to switch to its 3′→5′-exonuclease domain in order to degrade back to the nick position is important in maintaining a ligatable nick. This regulatory system has a built-in redundancy so that dysfunction of one of these activities can be tolerated in the cell. However, further dysfunction leads to uncontrolled strand displacement synthesis with deleterious consequences, as is revealed by genetic studies of exonuclease-defective mutants of S. cerevisiae Pol δ. These same parameters are also important for other DNA metabolic processes, such as base excision repair, that depend on Pol δ for synthesis.

Original languageEnglish
Pages (from-to)224-227
Number of pages4
JournalCell Cycle
Volume4
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • DNA polymerase
  • FEN1
  • Idling
  • Nick translation
  • Nuclease
  • Okazaki fragment
  • PCNA

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