Nucleic Acids Research, Vol 27, Issue 4 956-962, Copyright © 1999 by Oxford University Press
X Wu and Z Wang
Yeast Rad27 is a 5'-->3' exonuclease and a flap endo-nuclease. Apn1 is
the major apurinic/apyrimidinic (AP) endonuclease in yeast. The rad27
deletion mutants are highly sensitive to methylmethane sulfonate (MMS). By
examining the role of Rad27 in different modes of DNA excision repair, we
wish to understand why the cytotoxic effect of MMS is dramatically enhanced
in the absence of Rad27. Base excision repair (BER) of uracil-containing
DNA was deficient in rad27 mutant extracts in that (i) the Apn1 activity
was reduced, and (ii) after DNA incision by Apn1, hydrolysis of 1-5
nucleotides 3' to the baseless sugar phosphate was deficient. Thus, some AP
sites may lead to unprocessed DNA strand breaks in rad27 mutant cells. The
severe MMS sensitivity of rad27 mutants is not caused by a reduction of the
Apn1 activity. Surprisingly, we found that Apn1 endonuclease sensitizes
rad27 mutant cells to MMS. Deleting the APN1 gene largely restored the
resistance of rad27 mutants to MMS. These results suggest that unprocessed
DNA strand breaks at AP sites are mainly responsible for the MMS
sensitivity of rad27 mutants. In contrast, nucleotide excision repair and
BER of oxidative damage were not affected in rad27 mutant extracts,
indicating that Rad27 is specifically required for BER of AP sites in DNA.
ARTICLES
Relationships between yeast Rad27 and Apn1 in response to apurinic/apyrimidinic (AP) sites in DNA
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
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