"When you eliminate two GENEs that may work in concert to maintain good genomic order, you see things happen that are much more dramatic," said HHMI investigator Frederick Alt.

Researchers sifting through the indispensable machinery that senses and fixes broken DNA have discovered a new culprit that can induce instability in the genome and thereby set the stage for cancer to develop.

Studies in mice have shown that loss of H2AX, a gene that produces a protein called a histone that is part of the chromosomal structure, can tip the delicate balance of proteins that are curators of the human genome. When H2AX ceases to function properly, lymphomas and solid tumors can arise because errors in the genetic code are not always repaired correctly, according to the new research.

The finding may have important implications for understanding the origin of human cancers because a large number of human tumors are known to contain alterations in the region of chromosome 11 where the H2AX gene is located.

The research was reported in an article published in the August 8, 2003, issue of the jouRNAl Cell by Howard Hughes Medical Institute investigator Frederick Alt and colleagues at Children's Hospital in Boston and Harvard Medical School. Other co-authors are from the Tufts University School of Veterinary Medicine and Brigham and Women's

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