James Cleaver, PhD

Professor Emeritus
Department of Dermatology
Department of Pharmaceutical Chemistry
Research Overview: 

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.

Selected Publications
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. Developmental Biology, 208, 513-529,1999.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Human Genetics
Research Summary: 
DNA Repair Mechanisms and Human Disease