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Thomas Tan
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PhD student,
Biochemistry Department
Background:
- Research
Assistant, The Kuzell Institute for Arthritis and Infectious
Diseases, California Pacific Medical Center, San Francisco,
1996-1997
- BA
in Molecular and Cell Biology with an emphasis in Biochemistry,
University of California at Berkeley, 1996
- Undergraduate
research in the lab of Dr. Daniel E. Koshland, Jr. University
of California at Berkeley, 1995-1996
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Publications:
- Kolodziej
AF, Tan T, Koshland DE Jr. Producing positive, negative, and no
cooperativity by mutations at a single residue located at the
subunit interface in the aspartate receptor of Salmonella typhimurium.
Biochemistry. 1996 Nov 26;35(47):14782-92.
- Tan T, Chu
G. p53 Binds and activates the xeroderma pigmentosum DDB2 gene
in humans but not mice. Mol Cell Biol. 2002 May;22(10):3247-54.
Research:
Ultraviolet (UV) radiation exposure can lead to DNA lesions such
as cyclobutane pyrimidine dimers (CPDs) or 6-4 photoproducts. In
addition, chemicals such as benzo[a]pyrene (found in cigarettes)
and the chemotherapeutic drug, cisplatin, can lead to DNA damage.
Such forms of DNA damage are removed by nucleotide excision repair
(NER). The UV-damaged DNA binding protein (UV-DDB), which is composed
of the DDB1 and DDB2 proteins, can bind to damaged DNA. DDB2 is
important for global genomic repair of CPDs. Interestingly, rodent
fibroblast cells are deficient in GGR of CPDs, in contrast to human
cells. The human DDB2 gene is up regulated by p53. The p53 protein
is involved in DNA repair, apoptosis, and cell cycle arrest. UV
can activate p53, which in turn, can transcriptionally activate
the DDB2 gene. We found a p53-responsive binding site in the human
DDB2 gene. In contrast, the cognate site in the mouse DDB2 gene
was unresponsive to p53. We also showed that the entire mouse DDB2
gene is unresponsive to p53 and UV. It appears that rodents lack
p53 regulation of their DDB2 gene and subsequently lack GGR of CPDs
in their skin. This might be explained by the fact that rodents
are nocturnal animals and have fur to shield them from UV radiation.
Interestingly, mice express DDB2 in the liver, where detoxification
of chemicals takes place.We are currently investigating the role
of DDB2 in the repair of chemical damage.
Hobbies: Racquetball, basketball, soccer, softball, running,
weight training, indoor rock climbing, volleyball, bowling, dancing,
listening to music, helping Joe gather free food.
Home
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