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Faculty
 Michael R. Gryk
Assistant Professor of Molecular, Microbial & Structural Biology
gryk@uchc.edu
The focus of our laboratory is the use of NMR spectroscopy as a tool
for macromolecular characterization. Our studies currently involve DNA
repair proteins of relatively large molecular weight for NMR
spectroscopy (20-70 kDa). Current methods to overcome the difficulties
inherent in studying these large systems include extensive labeling
using stable isotopes and the use of TROSY-based pulse sequences. A
critical mission of the lab is the facility approach to NMR, such that
as advancements are made, they are tailored for ease-of-use both
internally and externally when possible.
Base Excision Repair
Intracellular repair of DNA damage caused by endogenous or exogenous
agents is critical for thwarting the onset of disease. This is why
higher organisms have evolved several repair pathways to prevent
localized DNA lesions from leading to more harmful genetic defects and
regulatory-induced diseases such as cancer. The base excision repair (BER)
pathway is one mammalian pathway for repairing short stretches of
nucleotide damage. Repair pathways include several DNA-specific enzymes,
such as glycosylases, endonucleases, polymerases, and ligases. An
additional protein involved in the regulation of BER, X-ray cross
complementing protein 1 (XRCC1), has no known enzymatic activity, but
rather serves as a scaffold in the recruitment and organization of the
other BER enzymes. XRCC1 is the only BER protein demonstrated to
interact with enzymes in each step of the repair pathway and its health
importance is underscored by the disease phenotypes of polymorphic amino
acid substitutions. The long-term goal of our research is to elucidate
the hierarchy of interactions responsible for the structural role of
XRCC1 in the BER machinery.
Structural Biology Facility
Structural Biology Tools
Publications
Selected Publications:
Marintchev, A., Gryk, M.R., and Mullen, G.P. (2003) Site-Directed
Mutagenesis Analysis of the Structural Interaction of the
Single-Strand-Break Repair Protein, X-ray Cross-Complementing Group 1,
with DNA Polymerase b.
Nucleic Acids Res., 31, 580-588.
Gryk, M.R., Marintchev, A., Maciejewski, M.W., Robertson, A., Wilson,
W.H., and Mullen, G.P. (2002) Mapping of the interaction interface of
DNA Polymerase b
with XRCC1. Structure, 10, 1709-1720.
Maciejewski, M.W., Shin, R., Pan, B., Marintchev, A., Denninger, A.,
Mullen, M.A., Chen, K., Gryk, M.R., and Mullen, G.P. (2001). Solution
structure of a viral DNA repair polymerase. Nature Struct. Biol.
8, 936-941.
Marintchev, A., Mullen, M.A., Maciejewski, M.W., Pan, B., Gryk, M.R.,
and Mullen, G.P. (1999). Solution structure of the single-strand break
repair protein XRCC1 N-terminal domain. Nature Struct. Biol. 6,
884-893. |
