Timing of development, metabolic regulation, and longevity are crucial elements in optimizing physiological functions to, and within, our environment. The synchronization of our internal clocks to the twenty-four hour day of our environment aids in anticipatory and protective measures on the molecular level. Dysregulation of this internal clock, known as the circadian clock, has been linked to various cancers, diabetes and heart failure. Mental ailments such as alcoholism and bipolarism can be magnified through dysregulation of our circadian rhythms. The output of circadian time keeping is still being explored, including the link to longevity. To further our understanding of clock functions through molecular structure, comparisons between biological time keeping methods are vital. On the molecular level of the circadian clock, one of the core negative feedback loop proteins is PERIOD. The complex timing of PERIOD transcription and protein accumulation directly contributes to setting the circadian clock. Within PERIOD protein, the functions of the homo- and heterodimerizing PERIOD-ARNT-SIM (PAS) domain to facilitate nuclear localization, and possibly many of the PERIOD output functions, are still being understood. Another protein that contains this canonical PAS domain is the nematode C. elegans development timing protein LIN-42. Although C. elegans are not known to have circadian rhythms, LIN-42 shares many motif and functional similarities to PERIOD. The development of C. elegans larva is repressively regulated, or gated, by LIN-42. Additionally, LIN-42 regulates entry into quiescent states during larval devolvement when environmental conditions are stressful. Considering the functions of LIN-42 within development of specialized stem cells, known as seam cells, and the recent discovery of the functions of PERIOD within the development of our own stem cells; a molecular comparison of LIN-42 and PERIOD will facilitate our understanding of the associated output functions of these proteins. Specifically the N-terminal regions of PER and LIN-42 share well-folded structural domains, and are the focus of this thesis. The forms of PERIOD and LIN-42 that share the most sequence and functional homology are PER2 and LIN-42b. Direct comparison of the similarities and differences between these two proteins on the molecular level will shed light on biological time keeping.
|Advisor:||Rubin, Seth M.|
|Commitee:||Partch, Carrie L.|
|School:||University of California, Santa Cruz|
|School Location:||United States -- California|
|Source:||MAI 52/04M(E), Masters Abstracts International|
|Subjects:||Biochemistry, Physical chemistry, Biomedical engineering|
|Keywords:||Circadian, Developmental, Lin-42, Molecular structure, Period, Timing|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be