Intellectual Merit: How do cells ensure that chromosomes are properly separated each time they divide? How do cells respond to damaging environmental conditions? What is the impact that these conditions have on the regulation of cell division? This project will contribute to find answers to these questions by investigating the function of the transcription factor Cin5/Yap4 in the bakers yeast Saccharomyces cerevisiae. Although discovered as a gene involved in the prevention of chromosome instability, CIN5 has been mainly studied as a stress-responsive gene: It functions regulating the expression of genes involved in the response to hyperosmotic or oxidative conditions, heat, presence of heavy metals, DNA damage, etc. Interestingly, previous studies have also determined that Cin5 associates moderately with Cdc28 and strongly with Cak1, two kinases that are crucial regulators of the cell cycle. One of the main goals of this research is to determine the effects of these associations. Both Cdc28 and Cak1 regulate mitotic progression and cdc28CST mutants have been isolated that display chromosome instability. It is then possible that the Cin5~Cdc28 and/or Cin5~Cak1 interactions are important to ensure proper separation of chromosomes. In one scenario, Cak1 and Cdc28 kinases might regulate Cin5 function, stability or localization via direct association and/or phosphorylation. Alternatively, binding by Cin5 could also affect the kinases by modulating their activities, substrate specificities and/or localizations. The authors will perform experiments to test each of these possibilities and further, determine how Cin5's mitotic functions relate to those in the stress response.
Broader Impacts: In order to encourage the early participation of undergraduates in research, a program will be developed for the students enrolled in the BIO140 class, Structure and Organization of the Cell, at UTK. Early in the spring semester, the students will be asked to volunteer to collaborate with the PI and her laboratory during the summer period. All minority students will be particularly encouraged to apply. Two students will be selected to work with the PI and graduate students designing and performing experiments, and analyzing the results. By working full time during the summer months (stipends will be provided), the undergraduates will get research training, and have the opportunity to apply what they are learning in their classes, and interact with personnel in the PI's and other laboratories. The students will be asked to present a PowerPoint-based seminar to the group of students taking BIO140 the following year. It is anticipated that by listening to their colleagues, the students in the class will recognize the feasibility and advantages of getting involved in research, and get a better appreciation of Science and the topics discussed in class. It is expected that the experiences gained with the implementation of this program will be the basis to develop a more comprehensive one, involving several research laboratories and eventual REU funding.
