Constance NugentDivisional Dean of Student Academic AffairsCNAS Deans Office Dept connienu@ucr.edu(951) 827-7294
Analyzing the Role of Yeast Telomere Capping Proteins in Coordinating Terminal Replication
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AWARD NUMBER
004844-004
FUND NUMBER
22269
STATUS
Closed
AWARD TYPE
3-Grant
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AWARD EXECUTION DATE
5/22/2012
BEGIN DATE
9/1/2010
END DATE
8/31/2013
AWARD AMOUNT
$199,999
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Sponsor Information
SPONSOR AWARD NUMBER
SPONSOR
SPONSOR TYPE
FUNCTION
Organized Research
PROGRAM NAME
Proposal Information
PROPOSAL NUMBER
10072202
PROPOSAL TYPE
New
ACTIVITY TYPE
Basic Research
PI Information
PI
Nugent, Connie
PI TITLE
Other
PI DEPTARTMENT
Molecular, Cell & Systems Bio
PI COLLEGE/SCHOOL
College of Nat & Agr Sciences
CO PIs
Project Information
ABSTRACT
Intellectual Merit. Maintaining the genome in the form of linear chromosomes poses significant challenges for eukaryotic cells. In particular, how to fully duplicate the chromosome termini (telomeres) and how to prevent sequence loss or inappropriate rearrangements at telomeres are critical issues. Key factors involved in solving these problems include the telomerase enzyme, which adds short G-rich repeats to one DNA strand of the telomere, and capping proteins that bind to telomeric sequences. Telomerase compensates for loss of telomeric sequences during replication, while capping proteins afford protection from enzymes that would otherwise degrade, unwind, or inappropriately recombine the ends. Interestingly, the DNA replication machinery, and the polymerase alpha-primase complex (Pol alpha) in particular, has been shown to have functional and physical connections with both telomerase and telomere capping activities. Based on this, the goal of this project is to understand at a molecular level how the function of telomere capping proteins and telomerase are coordinated with the DNA replication machinery. The budding yeast, Saccharomyces cerevisiae, will be used to investigate three issues that are relevant to this goal. First, do the telomere capping proteins Cdc13, Stn1 and Ten1 recruit Pol alpha; to newly extended telomeres? Second, do Cdc13, Stn1 and Ten1 enhance terminal replication fork progression or stability? Third, does Pol alpha; negatively regulate the processivity of telomerase? Answers to these questions have the potential to significantly expand our understanding of the mechanisms that coordinate telomere replication and telomere capping, and will undoubtedly provide insights that can be further tested in other organisms. Broader Impacts. Undergraduate and graduate students will carry out this project and participate in weekly presentations and discussions of experiments and related literature. The findings will be shared through participation of the students in local, national, and international conferences as well as publication in peer-reviewed journals. Since a relatively large proportion of the student population at UCR comprises underrepresented groups in science, increasing the opportunities for hands-on research will help to broaden the participation of these groups in science, exposing them to the excitement of discovery.(Abstract from NSF)
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