Genetics, Vol. 166, 1651-1659, April 2004, Copyright © 2004

EXO1 Contributes to Telomere Maintenance in Both Telomerase-Proficient and Telomerase-Deficient Saccharomyces cerevisiae

Alison A. Bertucha,b and Victoria Lundblada
a Department of Molecular and Human Genetics, Hematology/Oncology Section, Baylor College of Medicine, Houston, Texas 77030
b Department of Pediatrics, Hematology/Oncology Section, Baylor College of Medicine, Houston, Texas 77030

Corresponding author: Alison A. Bertuch, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030., abertuch{at}bcm.tmc.edu (E-mail)

Communicating editor: L. PILLUS

Previous work in budding yeast has indicated that telomeres are protected, at least in part, from the action of Exo1, which degrades the C-rich strand of partially uncapped telomeres. To explore this further, we examined the consequences of Exo1-mediated activity in strains that lacked Ku, telomerase, or both. Loss of Exo1 partially rescued the telomere length defect in a yku80{Delta} strain, demonstrating that exonuclease action can directly contribute to telomere shortening. The rapid loss of inviability displayed by a yku80{Delta} est2{Delta} strain was also partially alleviated by an exo1{Delta} mutation, further supporting the proposal that Exo1 is one target of the activities that normally protect wild-type telomeres. Conversely, however, Exo1 activity was also capable of enhancing telomere function and consequently cell proliferation, by contributing to a telomerase-independent pathway for telomere maintenance. The recovery of recombination-dependent survivors that arose in a yku80{Delta} est2{Delta} strain was partially dependent on Exo1 activity. Furthermore, the types of recombination events that facilitate telomerase-independent survival were influenced by Exo1 activity, in both est2{Delta} and yku80{Delta} est2{Delta} strains. These data demonstrate that Exo1 can make either positive or negative contributions to telomere function and cell viability, depending on whether telomerase or recombination is utilized to maintain telomere function.





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