Cell cycle checkpoint control in budding yeast Saccharomyces cerevisiae.
AuthorKiser, Gretchen Louise.
Committee ChairWeinert, Ted
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractMultiple checkpoint controls ensure that later cellular events are not initiated until previous cellular events have been successfully completed. Our laboratory studies the checkpoint at the G2/M boundary that ensures the integrity of chromosome transmission by blocking mitosis until DNA synthesis and repair is completed. The checkpoint-dependent cell division arrest is one of several prominent responses to DNA damage, which also includes transcriptional induction of damage-inducible genes and DNA repair. I undertook three projects that explore several aspects of the damage response: (1) I further characterized the checkpoint gene RAD24, in that I showed that RAD24 function has G2 phase-specificity after damage and that RAD24 contributes to genomic stability; (2) I evaluated the nature of the damage signal from UV-irradiation that elicits a checkpoint-dependent cell cycle arrest; and (3) I established a transcriptional role for some of the checkpoint genes. In addition, I characterized a gene that encodes a novel elongation factor-type GTPase. Upon examination of the checkpoint-dependent delay following UV-irradiation in a mutant defective for incision of pyrimidine dimers, I found that processing of DNA damage, i.e. dimer-incision, is necessary to generate an appropriate damage signal. Processing of damage may be a general property of the damage response and may involve the checkpoint proteins. I found that some checkpoint genes have an additional role in a complex transcriptional induction response to DNA damage. Primarily, I found: (i) mec1 and mec2 mutants are defective for DNA damage-induction of the RNR3 gene, whereas the other checkpoint mutants appear to play less of a role; (ii) all the checkpoint mutants are proficient for transcriptional induction UBI4; (iii) rad17 mutants, and to a lesser degree mec1 and mec2 mutants as well, are defective for damage-induction of DDR48; (v) transcription of the RAD17, RAD24, MEC1, and MEC2 (but not the RAD9) checkpoint genes is damage-inducible and MEC1 is required for the transcriptional induction of the MEC1 and MEC2 genes, but not the RAD17 or RAD24 genes. I suggest that their transcriptional function ties the checkpoint proteins to DNA repair, as damage-inducible transcriptional induction probably functions to augment repair.
Degree ProgramMolecular and Cellular Biology