Efficient DNA base excision repair in ataxia telangiectasia cells

Enrico Cappelli, Ottavio Rossi, Luciana Chessa, Guido Frosina

Research output: Contribution to journalArticle

Abstract

Ataxia telangiectasia (A-T) cells are sensitive to a broad range of free-radical-producing and alkylating agents. Damage caused by such agents is in part repaired by base excision [base excision repair (BER)]. Two BER pathways have been demonstrated in mammalian cells: a single-nucleotide-insertion pathway and a long-patch pathway involving resynthesis of 2-10 nucleotides. Although early studies failed to detect DNA-repair defects in A-T cells exposed to ionizing radiation and radiomimetic agents, more recent experiments performed in non-dividing A-T cells and the demonstrated interaction of the A-T-mutated protein (ATM) with the BRCA1 gene product suggest that a DNA-repair defect may underlie, at least in part, the radiation sensitivity in A-T cells. We have analysed BER of a single abasic site or a single uracil in two A-T families, using an in vitro BER system. In both families, the mutation involved was homozygous and completely inactivated the ATM protein. No difference was observed between affected individuals and heterozygous or homozygous wild-type relatives in their capacity to perform DNA repair by either one-nucleotide insertion or the long-patch pathway. Hence, the putative DNA-repair defect in A-T cells, if any, does not involve BER.

Original languageEnglish
Pages (from-to)6883-6887
Number of pages5
JournalEuropean Journal of Biochemistry
Volume267
Issue number23
DOIs
Publication statusPublished - 2000

Fingerprint

Ataxia Telangiectasia
DNA Repair
Repair
DNA
Cells
Nucleotides
Defects
Ataxia Telangiectasia Mutated Proteins
BRCA1 Protein
Uracil
Alkylating Agents
Radiation Tolerance
Ionizing radiation
Ionizing Radiation
Cell Communication
Free Radicals
Proteins
Radiation
Mutation

Keywords

  • Abasic sites
  • Ataxia telangiectasia
  • DNA base excision repair
  • In vitro
  • Uracil

ASJC Scopus subject areas

  • Biochemistry

Cite this

Efficient DNA base excision repair in ataxia telangiectasia cells. / Cappelli, Enrico; Rossi, Ottavio; Chessa, Luciana; Frosina, Guido.

In: European Journal of Biochemistry, Vol. 267, No. 23, 2000, p. 6883-6887.

Research output: Contribution to journalArticle

Cappelli, Enrico ; Rossi, Ottavio ; Chessa, Luciana ; Frosina, Guido. / Efficient DNA base excision repair in ataxia telangiectasia cells. In: European Journal of Biochemistry. 2000 ; Vol. 267, No. 23. pp. 6883-6887.
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