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Endogenous DNA abasic sites cause cell death in the absence of Apn1, Apn2 and Rad1/Rad10 in Saccharomyces cerevisiae
Author(s) -
Guillet Marie,
Boiteux Serge
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.11.2833
Subject(s) - biology , saccharomyces cerevisiae , ap site , dna , dna damage , dna repair , endogeny , genetics , saccharomyces , microbiology and biotechnology , yeast , biochemistry
In Saccharomyces cerevisiae , mutations in APN1, APN2 and either RAD1 or RAD10 genes are synthetic lethal. In fact, apn1 apn2 rad1 triple mutants can form microcolonies of ∼300 cells. Expression of Nfo, the bacterial homologue of Apn1, suppresses the lethality. Turning off the expression of Nfo induces G 2 /M cell cycle arrest in an apn1 apn2 rad1 triple mutant. The activation of this checkpoint is RAD9 dependent and allows residual DNA repair. The Mus81/Mms4 complex was identified as one of these back‐up repair activities. Furthermore, inactivation of Ntg1, Ntg2 and Ogg1 DNA N ‐glycosylase/AP lyases in the apn1 apn2 rad1 background delayed lethality, allowing the formation of minicolonies of ∼10 5 cells. These results demonstrate that, under physiological conditions, endogenous DNA damage causes death in cells deficient in Apn1, Apn2 and Rad1/Rad10 proteins. We propose a model in which endogenous DNA abasic sites are converted into 3′‐blocked single‐strand breaks (SSBs) by DNA N ‐glycosylases/AP lyases. Therefore, we suggest that the essential and overlapping function of Apn1, Apn2, Rad1/Rad10 and Mus81/Mms4 is to repair 3′‐blocked SSBs using their 3′‐phosphodiesterase activity or their 3′‐flap endonuclease activity, respectively.