A major contribution to understanding human health
risks from environmental carcinogens has come from studies in human
genetic diseases that show increased susceptibility to genotox-ic
agents, often associated with defective DNA repair. Xeroderma pigmentosum
and related diseases, which fail to repair damage from ultraviolet
light and other DNA damaging agents, has played a pivotal role in
relating DNA damage and repair to carcinogenesis. These studies have
also revealed a fundamental linkage between repair, DNA replication,
cell cycle control, p53 function and gene transcription. DNA repair
is now recognized as of major importance in cancers of the skin, breast,
colon, and hematopoeitic systems. We have recently found that rad51-dependent
recombination is stimulated by DNA damage in a p53-dependent manner,
and are presently investigating potential linkage to the breast cancer
Brca1 and 2 genes. We are also cloning several genes involved in DNA
replication-arrest and genomic instability and developing transgenic
knockout animals that are models for human DNA repair deficient diseases. |
States,J.C., McDuffie,E.R., Mytrand,S.P., and
Cleaver, J.E. The distribution of mutations in the human XPA gene
and their relationships to the functional regions of the DNA damage
recognition protein.Human Mutation 12:103-113, 1998.
Cleaver,J.E., Afzal,V.,Feeney,L.,McDowell,M.L.,Sadinski,W.,Volpe,J.P.G.,Busch,D.B.,
Coleman,D.M.,Ziffer,D.W.,Yu,Y.,Nagasawa,H.,Little,J.B. Increased
ultraviolet sensitivity and chromosomal instability related to p53
function in the xeroderma pigmentosum variant. Cancer Research 59:1102-1108,1999.
Tebbs, R.S., Flannery, M., Meneses, J.J., Hartmann,A.J., Tucker,
J.D., Thompson, L.H., Cleaver, J.E., and Pedersen R.A. Requirement
for the XRCC1 DNA base excision repair gene during early mouse development.
Development al Biology, 208, 513-529,1999.
information last updated February 2003 |
Biomedical Sciences (BMS) Graduate Program
