William M. Bonner

Biography

Dr. Bonner received his Ph.D. from Harvard University in Biochemistry and Molecular Biology. This was followed by postdoctoral studies at Oxford University and the MRC Laboratories in Cambridge, England. While at Cambridge, he became interested in histones and continued this work when he arrived at the NIH in 1974 as a Staff Fellow in the National Institute of Child Health and Human Development. Two years later he moved to the Laboratory of Molecular Pharmacology in NCI. In 1980 he identified two specialized variants of the histone H2A family, which were given the names of H2AX and H2AZ. Continuing his work on various aspects of histone metabolism during the 1980s and early 90s, he uncovered in 1998 the relationship between DNA double strand breaks (DSBs) and the phosphorylated form of histone H2AX, named γ-H2AX. Upon introduction of a DSB into DNA, many hundreds of H2AX molecules become phosphorylated within minutes in the chromatin flanking the break site, thus providing a rapid and highly amplified detection system and a focus for the accumulation of many other proteins involved in DNA repair and chromatin remodeling. This finding greatly facilitated research into DNA damage by permitting the identification of individual DNA DSBs in cells in situ, and by enabling researchers to investigate DSBs not only as a result of ionizing radiation but also as a necessary step in other processes such as the development of the immune system, in sperm formation and in aging. Dr. Bonner and others have found that many anti-cancer agents induce the formation of γ-H2AX foci, an attribute that gives γ-H2AX a potential role as a biodosimeter to monitor patient response to drug treatment and as a rapid screen of compounds for DNA damaging agents for potential new anti-cancer drugs.

Research Interest

Translational project investigating the parameters necessary to make H2AX a useful biodosimeter in humans and other animals; The use of γ-H2AX to probe for interactions between cells in animals; Structure and dynamism of the γ-H2AX focus; Chromosome Biology