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Molecular Carcinogenesis: Mechanisms of DNA Repair and Mutagenesis in Mammalian Cells
Research in the Laboratory of Chemical Biology (LCB),
for which Dr Grollman serves as Director, focuses on
the biological consequences of DNA damage with specific reference to molecular
mechanisms of DNA replication, mutagenesis, and DNA repair. Research in the LCB
was instrumental in establishing the mechanism of action of bleomycin and in
defining an important error-avoidance pathway that protects cells against
mutations resulting from miscoding effects of oxidative DNA damage. He
and his collaborators established the three-dimensional structures of DNA
glycosylases and DNA polymerases bound to site-specifically modified DNA,
thereby correlating the molecular structure of damaged DNA with enzymatic
function. Current research focuses on molecular and cellular mechanisms
involved in the nephrotoxicity of the human carcinogen, aristolochic acid.
Zaika EI, Perlow RA, Matz E, Broyde S, Gilboa R, Grollman AP, Zharkov
DO (2004). Substrate
discrimination by formamidopyrimidine-DNA glycosylase: a mutational
analysis. J Biol Chem. 279 4849-61.
Freisinger E, Grollman AP, Miller H, Kisker C (2004). Lesion
(in)tolerance reveals insights into DNA replication fidelity. EMBO J. 23 1494-505.
Miller H, Grollman AP (2003). DNA
repair investigations using siRNA. DNA repair 2 759-63.
Rosenquist TA, Zaika E, Fernandes AS, Zharkov DO, Miller H,
Grollman AP (2003). The
novel DNA glycosylase, NEIL1, protects mammalian cells from
radiation-mediated cell death. DNA repair 2 581-91.
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