Biochemistry and Molecular Biology
766 Irving Avenue
Syracuse, NY 13210
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Phone: 315 464-5127
Fax: 315 464-8750
Name: Patricia M Kane, PhD, Chair
The Department of Biochemistry and Molecular Biology offers a highly collaborative research community and an excellent training environment for young scientists.
The field of biochemistry and molecular biology has been transformed in the past decade with the sequencing of the human genome and genomes of other organisms, atomic resolution structures for many important macromolecules, and technological advances that allow integration of this information to address fundamental questions about the structure and function of cells and organisms. These developments create unprecedented opportunities for scientific research and understanding of human health and disease.
- Oxr1 - a novel regulator of V-ATPase
The vacuolar ATPase (V-ATPase) is a highly conserved rotary motor proton pump that plays an essential role in cellular housekeeping functions. Not surprisingly, V-ATPase activity (or loss thereof) has been linked to several disease states including renal tubular acidosis, osteoporosis, neurodegeneration, and cancer. V-ATPase is made of two subcomplexes: a cytosolic V1 that carries out ATP hydrolysis, and a membrane bound Vo that is responsible for proton translocation. The enzyme’s proton pumping function is regulated by a unique process called “reversible disassembly”, wherein V1 dissociates from Vo in a for example nutrient dependent manner. To understand V-ATPase’s role in health and disease, the Wilkens lab studies the structure and mechanism of the enzymes from yeast and human. Read more...
- Implication of Organelle pH Regulation by Phosphoinositides through “Zip Codes” in Vacuolar H+-ATPase
The organelles of the secretory and endocytic pathway include the ER, Golgi network, endosomes and lysosomes or, the lysosome like yeast vacuole. All of these organelles maintain a distinct and tight range of pH. The vacuole/lysosome (pH 4/5.5) is the most acidic compartment in eukaryotes, whereas the Golgi is relatively alkaline (pH 6.6). Variation in pH largely affects the function of these organelles. For example, alkaline vacuole/lysosome are deficient in autophagy, Golgi pH regulates its ability to glycosylate proteins and failure to maintain endosomal pH perturbs with its ability to recycle receptors to the Plasma membrane or, the trans-Golgi. Read more...
- Structure of Lipid Nanodisc-reconstituted Vacuolar ATPase Proton Channel: Defining the Interaction of Rotor and Stator
The Wilkens lab focuses on the structural characterization of the vacuolar ATPase (or V-ATPase) in order to elucidate its mechanism of activity and regulation. V-ATPase is a ubiquitous eukaryotic rotary proton pump that is foiund in the endomembrane system and serves to acidify a variety of intracellular compartments as well as the extracellular space in higher eukaryotes. V-ATPase is essential in animals; full loss of activity is embryonic lethal and partial loss of function has been associated with various human diseases including osteoporosis, male infertility, sensorineural deafness, diabetes and various cancers. Read more...
- The Smc5/6 complex at the crossroads of DNA replication, repair and recombination
Due to the imperfect “steric gate”, DNA polymerase intrinsically mis-incorporates not only mismatched deoxyribonucleosides monophosphates but also ribonucleoside monophosphates (rNMPs) during DNA replication at a rate of 10−7 and 4 × 10−4, respectively (1). To repair these DNA damages it requires specific recognition and excision proteins to remove the damage and create a single-stranded DNA (ssDNA) gap, followed by the DNA polymerase to fill the gap and the DNA ligase to seal the nick. Read more...
- New class of p53-reactivating compounds provides novel mechanism to treat cancer - August 2015
The "Guardian of the Genome," p53, is a tumor suppressing transcription factor that has long been recognized as perhaps the most important protein in human cancer. Approximately 50% of human cancers harbor mutations in p53, which render the protein inactive and unable to protect the cells from cancerous transformation. Read more...
- Mechanism of Ant1-induced human diseases unraveled by the Chen lab - July 2015
Mitochondria are the powerhouses of the cell. About 90% of the energy that cells need is produced in the form of ATP by the OXPHOS apparatus on the mitochondrial inner membrane. After it's synthesis by the F0F1 ATP-synthase, ATP is exported out of mitochondria via adenine nucleotide translocase (Ant) by exchanging with the cytosolic ADP. Read more...
- Using disease-associated mutations to understand the biochemical regulation of a multi-subunit histone methyltransferase complex - June 2014
Eukaryotic DNA is compacted into chromatin, which must be continually remodeled to allow for DNA processes such as transcription. The basic repeating unit of chromatin, the nucleosome, is composed of an octomer of histone proteins around which 147 base pairs of DNA is wrapped. One way chromatin remodeling is achieved is by posttransitional modification of histones. Read more...