The block of DNA polymerase delta strand displacement activity by an abasic site can be rescued by the concerted action of DNA polymerase beta and Flap endonuclease 1

J Biol Chem. 2009 May 22;284(21):14267-75. doi: 10.1074/jbc.M900759200. Epub 2009 Mar 27.


Abasic (AP) sites are very frequent and dangerous DNA lesions. Their ability to block the advancement of a replication fork has been always viewed as a consequence of their inhibitory effect on the DNA synthetic activity of replicative DNA polymerases (DNA pols). Here we show that AP sites can also affect the strand displacement activity of the lagging strand DNA pol delta, thus preventing proper Okazaki fragment maturation. This block can be overcome through a polymerase switch, involving the combined physical and functional interaction of DNA pol beta and Flap endonuclease 1. Our data identify a previously unnoticed deleterious effect of the AP site lesion on normal cell metabolism and suggest the existence of a novel repair pathway that might be important in preventing replication fork stalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism
  • DNA Damage*
  • DNA Polymerase III / metabolism*
  • DNA Polymerase beta / metabolism*
  • DNA Replication*
  • Flap Endonucleases / metabolism*
  • Humans
  • Models, Biological
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding
  • Templates, Genetic


  • Proliferating Cell Nuclear Antigen
  • DNA
  • POLD1 protein, human
  • DNA Polymerase III
  • DNA Polymerase beta
  • Flap Endonucleases