Abstract

Photolyase and cryptochrome are evolutionarily and structurally related flavoenzymes that catalyze two entirely different biological reactions. Photolyase is an enzyme that uses the energy of blue light to reverse UV-induced DNA photoproducts and thus prevents the mutagenic and lethal effects of UV. Cryptochrome regulates the circadian clock in animals, growth and development in plants, and performs an unknown function in bacteria. The basic photochemical reaction carried out by photolyase is relatively well understood but the photocatalytic function of cryptochrome is not known. The goal of this research is to understand how photolyase and cryptochrome perform their distinct functions. Towards this aim, the following experiments will be conducted. ? 1. We will characterize the photoreceptor function and the functional dynamics of the excited states of the photolyase/cryptochrome family by ultrafast spectroscopy. ? 2. We will investigate the mechanisms of signal transduction of animal, plant and microbial cryptochromes. ? 3. We will analyze the light-independent function of cryptochrome in the circadian clock and determine the effects of clock disruption on DNA damage checkpoints at the cellular level and on tumorigenesis in mice. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031082-24
Application #
7258898
Study Section
Special Emphasis Panel (ZRG1-GGG-F (05))
Program Officer
Ikeda, Richard A
Project Start
1982-08-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
24
Fiscal Year
2007
Total Cost
$549,265
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Krishnaiah, Saikumari Y; Wu, Gang; Altman, Brian J et al. (2017) Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism. Cell Metab 25:961-974.e4
Chiou, Yi-Ying; Yang, Yanyan; Rashid, Naim et al. (2016) Mammalian Period represses and de-represses transcription by displacing CLOCK-BMAL1 from promoters in a Cryptochrome-dependent manner. Proc Natl Acad Sci U S A 113:E6072-E6079
Jang, Hagoon; Lee, Gha Young; Selby, Christopher P et al. (2016) SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding. Nat Commun 7:12180
Adar, Sheera; Hu, Jinchuan; Lieb, Jason D et al. (2016) Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis. Proc Natl Acad Sci U S A 113:E2124-33
Hu, Jinchuan; Adar, Sheera; Selby, Christopher P et al. (2015) Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution. Genes Dev 29:948-60
Sancar, Aziz; Lindsey-Boltz, Laura A; Gaddameedhi, Shobhan et al. (2015) Circadian clock, cancer, and chemotherapy. Biochemistry 54:110-23
Tan, Chuang; Liu, Zheyun; Li, Jiang et al. (2015) The molecular origin of high DNA-repair efficiency by photolyase. Nat Commun 6:7302
Ozturk, Nuri; Selby, Christopher P; Zhong, Dongping et al. (2014) Mechanism of photosignaling by Drosophila cryptochrome: role of the redox status of the flavin chromophore. J Biol Chem 289:4634-42
Ye, Rui; Selby, Cristopher P; Chiou, Yi-Ying et al. (2014) Dual modes of CLOCK:BMAL1 inhibition mediated by Cryptochrome and Period proteins in the mammalian circadian clock. Genes Dev 28:1989-98
Annayev, Yunus; Adar, Sheera; Chiou, Yi-Ying et al. (2014) Gene model 129 (Gm129) encodes a novel transcriptional repressor that modulates circadian gene expression. J Biol Chem 289:5013-24

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