Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have identified a gene that plays an important role in preventing tumors in mice. In a study, the researchers demonstrate that reducing or eliminating the H2AX gene in mice that lack p53, a well-known tumor suppressor gene, causes an increase in the number of tumors that develop.

"This work demonstrates that H2AX plays an important role in maintaining the integrity of cells' genetic information, and therefore in preventing tumor formation," said Andre Nussenzweig, of NCI's Experimental Immunology Branch, the lead researcher on the study. "Both copies of the H2AX gene are required for optimal protection against tumors."

The work by the NCI research team is in agreement with a similar study led by Fred Alt, at Harvard University, which also demonstrates that H2AX cooperates with p53 to ensure that damaged cells do not grow out of control and promote tumor development.

The protein produced by the H2AX gene belongs to a class of molecules known as histones, which are involved in the packaging of DNA inside the cell. About five years ago, scientists first recognized that the H2AX histone is involved in the cell's response to DNA damage - a discovery made by William Bonner, at NCI.

H2AX is activated when DNA molecules inside the cell are broken. Such breakage can be caused by external factors such as radiation, but also routinely occurs during normal cellular processes. Although breaks in DNA are necessary for some biological processes, it is essential that the breaks be repaired. If breaks remain when a cell divides, important genetic information located on the DNA molecules can be lost in some cells while other cells receive extra copies of certain genes.

One potential consequence of a loss or gain of genetic information is the development of cells whose growth is not properly regulated. Uncontrolled multiplication of these cells, in turn, can give rise to cancer. Because of its role in the repair of broken DNA molecules, H2AX helps maintain genomic integrity; for this reason, the NCI researchers speculated that mice without H2AX might develop more tumors than those with H2AX.

The researchers studied mice in which they had eliminated one or both of the two normal copies of the H2AX gene. They discovered that DNA in the cells of mice lacking H2AX was frequently broken and rearranged. If this type of damage occurred in regions of DNA critical for growth control, tumor formation could result. Surprisingly, however, mice lacking H2AX developed no tumors during the course of the experiment.