AP endonuclease-independent DNA base excision repair in human cells

Lee Wiederhold, John B. Leppard, Padmini Kedar, Feridoun Karimi-Busheri, Aghdass Rasouli-Nia, Michael Weinfeld, Alan E. Tomkinson, Tadahide Izumi, Rajendra Prasad, Samuel H. Wilson, Sankar Mitra, Tapas Hazra

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

The paradigm for repair of oxidized base lesions in genomes via the base excision repair (BER) pathway is based on studies in Escherichia coli, in which AP endonuclease (APE) removes all 3′ blocking groups (including 3′ phosphate) generated by DNA glycosylase/AP lyases after base excision. The recently discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the previously characterized OGG1 and NTH1, generate DNA strand breaks with 3′ phosphate termini. Here we show that in mammalian cells, removal of the 3′ phosphate is dependent on polynucleotide kinase (PNK), and not APE. NEIL1 stably interacts with other BER proteins, DNA polymerase β (pol β) and DNA ligase IIIα. The complex of NEIL1, pol β, and DNA ligase IIIα together with PNK suggests coordination of NEIL1-initiated repair. That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalMolecular Cell
Volume15
Issue number2
DOIs
StatePublished - Jul 23 2004

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DNA-(Apurinic or Apyrimidinic Site) Lyase
DNA Repair
Polynucleotide 5'-Hydroxyl-Kinase
DNA Glycosylases
DNA
Phosphates
DNA Breaks
DNA-Directed DNA Polymerase
Mammals
Genome
Escherichia coli
Proteins

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Wiederhold, L., Leppard, J. B., Kedar, P., Karimi-Busheri, F., Rasouli-Nia, A., Weinfeld, M., ... Hazra, T. (2004). AP endonuclease-independent DNA base excision repair in human cells. Molecular Cell, 15(2), 209-220. https://doi.org/10.1016/j.molcel.2004.06.003

AP endonuclease-independent DNA base excision repair in human cells. / Wiederhold, Lee; Leppard, John B.; Kedar, Padmini; Karimi-Busheri, Feridoun; Rasouli-Nia, Aghdass; Weinfeld, Michael; Tomkinson, Alan E.; Izumi, Tadahide; Prasad, Rajendra; Wilson, Samuel H.; Mitra, Sankar; Hazra, Tapas.

In: Molecular Cell, Vol. 15, No. 2, 23.07.2004, p. 209-220.

Research output: Contribution to journalArticle

Wiederhold, L, Leppard, JB, Kedar, P, Karimi-Busheri, F, Rasouli-Nia, A, Weinfeld, M, Tomkinson, AE, Izumi, T, Prasad, R, Wilson, SH, Mitra, S & Hazra, T 2004, 'AP endonuclease-independent DNA base excision repair in human cells', Molecular Cell, vol. 15, no. 2, pp. 209-220. https://doi.org/10.1016/j.molcel.2004.06.003
Wiederhold L, Leppard JB, Kedar P, Karimi-Busheri F, Rasouli-Nia A, Weinfeld M et al. AP endonuclease-independent DNA base excision repair in human cells. Molecular Cell. 2004 Jul 23;15(2):209-220. https://doi.org/10.1016/j.molcel.2004.06.003
Wiederhold, Lee ; Leppard, John B. ; Kedar, Padmini ; Karimi-Busheri, Feridoun ; Rasouli-Nia, Aghdass ; Weinfeld, Michael ; Tomkinson, Alan E. ; Izumi, Tadahide ; Prasad, Rajendra ; Wilson, Samuel H. ; Mitra, Sankar ; Hazra, Tapas. / AP endonuclease-independent DNA base excision repair in human cells. In: Molecular Cell. 2004 ; Vol. 15, No. 2. pp. 209-220.
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