Base excision repair pathway

Bennett, R.A., Wilson, D.M., 3rd, Wong, D., and Demple, B. (1997) Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway. Proc. Natl. Acad. Sci. USA 94, 7166-7169. 

FIGURE 25-23 DNA repair by the base-excision repair pathway. 

Seeberg E, Eide L, Bjoras M. The base excision repair pathway. Trends Biochem. Sci. 1995 20 391-397. 

One of the first important insights in the field of DNA repair was made after isolation of E. coli mutants with exceptional sensitivity to UV light [2] and subsequent mapping of mutations in genes designated uvrA, B, and C [3]. This led to the model of nucleotide excision repair [4,5]. Later the base excision repair pathway was exposed when Lindahl and coworkers [6,7] discovered a series of bacterial enzymes that recognized and removed modified nucleotides by a DNA N-glycosylase reaction. 

Dianov, G. and Lindahl, T. (1994) Reconstitution of the DNA base excision-repair pathway. Curr. Biol., 4, 1069-1076. 

Figure 13.11 Reaction sequence of the base excision repair pathway. The base excision repair (BER) pathway is exemplified for the uracil excision-repair reactions. Only the lesioned (e.g. uracil) part of one strand nucleotide structure of the dsDNA is shown. The excision of uracil by uracil DNA glycosylase without associated AP-lyase generally follows AP-endonuclease and 5 -deoxyribophosphodiesterase which cleave the nucleotide chain. The repair with N-glycosylase is associated with AP-lyase (P-elimination reaction catalyzed by AP-lyase converts the deoxyribose residue to aldehyde form) and 3 -phosphodiesterase. The single nucleotide gap is filled by DNA polymerase (dCTP is required to replace uracil) and DNA ligase...

Fig. 1. Base excision repair pathway for repair of DNA base damage. Base damage is indicated by the color red and an asterisk. The key enzymatic activities are indicated at each step, but some steps require proteins not indicated. Pol is an abbreviation for polymerase. (See Color Insert.)...

In eukaryotic cells, DNA damage may induce a several thousand fold stimulation of poly(ADP-ribose) metabolism. A few restrictions and rules apply yeast does not express such a response, and in all other eukaryotes tested so far, the most effective types of DNA damages are those that are substrates for the DNA base excision repair pathway. By far the largest amount of ADP-ribose is processed throi the catalytic domains of two nuclear enzymes poly(ADP-ribose)polymerase-l, (PARP-1), and its catabolic counterpart, poly(ADP-ribose)glycohydrolase (PARC). Other members of the growing PARP family may contribute to this metabolism, albeit to a much lesser extent and with mechanisms that await further elucidation (for reviews see refs. 1,2). 

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