The base excision repair (BER) pathway is generally considered to
repair damaged bases in four steps: (1) generation of an abasic (AP)
site by a damage-specific glycosylase, (2) cleavage of the DNA backbone
at the AP site by an endonuclease or lyase, (3) removal of the AP site
and creation of a small gap, and (4) DNA polymerase mediated filling-in
of the gap and ligation. We have mutationally blocked base excision
repair in yeast by eliminating the major AP endonuclease (Apn1p) plus
two glycosylases that have an associated lyase activity (Scr1p and
Scr2p). Surprisingly, such strains are not sensitive to oxidizing agents
that generate damage thought to be repaired via BER. These strains do,
however, become very sensitive to such damage if recombination also is
blocked by eliminating Rad52p. In the absence of exogenous DNA damage
BER-defective strains exhibit mitotic hyper-recombination and hyper-mutation phenotypes. The hyper-mutation phenotype of BER-defective
strains is dependent on Rev3p, a component of a translesion polymerase
involved in an error prone repair pathway. The hyper-recombination
phenotype of BER-defective strains is enhanced in the absence of Rev3p,
and the hyper-mutation phenotype of BER-defective strains is enhanced in
the absence of Rad52p. These data indicate that the BER, recombination
and error prone repair pathways compete for the repair of the same types
of DNA damage and suggest that recombination and lesion bypass are
efficient mechanisms for dealing with BER intermediates.
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