Faculty / Research
Masaaki Moriya, PhDResearch Professor
Ph.D., Nagoya University, Japan
Postdoctoral, National Institute of Genetics, Japan
Cellular responses to DNA damage and the mechanism for mutation induction by DNA damage
Cells are continuously exposed to exogenous and endogenous DNA-damaging agents.To overcome their deleterious effects and restore the genome integrity, cells have developed elaborate protection mechanisms against these agents.My research focuses on the cellular responses to DNA damage and the mechanism for mutation induction by DNA damage.Upon DNA damage, cells stop the progression of cell cycle and initiate the repair of DNA damage.After completion of repair, cells resume the cell cycle. However, damage occasionally escapes DNA repair.When this damage is involved in DNA replication, it often blocks the progression of DNA synthesis.Cells have developed a mechanism for overcoming this blocking by inducing a set of genes.DNA synthesis across damaged DNA, with or without the aid of induced proteins, is error-prone.This process leads to the introduction of mutations into our ?blue print,? contributing to the onset of cancer.Cells also employ error-free mechanisms to overcome this block by utilizing a sister DNA molecule that is generated from the undamaged complementary strand.These mechanisms are intricately regulated in cells.
A cutting-edge technology is currently used to study these subjects. A short piece of DNA containing a single, chemically-defined DNA damage is synthesized and incorporated into vector DNA.This modified DNA is then introduced into host cells, where various host proteins respond to the damage. My research covers the following subjects: (i) What is the mechanism for overcoming the synthesis block in bacteria, yeast and human cells?; (ii) What genes are involved in this mechanism?; (iii) What is the biochemical roles of these gene products?; (iv) How is DNA damage repaired?; and (v) how does DNA damage cause mutations? By studying these subjects, I hope to elucidate the cellular mechanisms for processing of and responding to DNA damage.
Moriya, M., Single-stranded shuttle phagemid for mutagenesis studies in mammalian cells: 8-oxoguanine in DNA induces targeted G:C?T:A transversions in simian kidney cells, Proc. Natl. Acad. Sci. USA 90, 1122-1126, 1993.
Grollman, A.P. and Moriya, M., Mutagenesis by 8-oxoguanine: an enemy within, Trends in Genetics 9, 246-249, 1993.
Moriya, M. and Grollman, A.P., Mutations of the mutY gene of Escherichia coli enhance the frequency of targeted G:C?T:A transversions induced by a single 8-oxoguanine residue in single-stranded DNA,Mol. Gen. Genet. 239, 72-76, 1993.
Moriya, M., Zhang, W., Johnson, F, and Grollman, A.P., Mutagenic potency of exocyclic DNA adducts: marked differences between Escherichia coli and simian kidney cells, Proc. Natl. Acad. Sci. USA 91, 11899-11903, 1994.
Pandya, G. and Moriya, M., 1, N6-ethenodeoxyadenosine, a DNA adduct highly mutagenic in mammalian cells, Biochemistry 35, 11487-11492, 1996.
Moriya, M., Spiegel, S., Felnandes, A., Liu, T.-M., Geacintov, N., and Grollman, A.P., Fidelity of translesional synthesis past benzo[a]pyrene-N2-deoxyguanosine adduct: marked effects of host cell, neighboring base, and chirality, Biochemistry 35, 16646-16651, 1996.