Molecular Biology

The Perils of Histone Loss

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Science  29 Aug 2003:
Vol. 301, Issue 5637, pp. 1159
DOI: 10.1126/science.301.5637.1159a

Left unattended, the many types of damage that afflict genomic DNA can have dire consequences for the mammalian cell. Double-strand breaks, for example, are potent substrates for chromosomal rearrangements that can push a cell toward malignancy. Among the molecular players implicated in the cellular response to these breaks is a histone variant called H2AX, which—together with DNA repair enzymes and signaling proteins—accumulates nearby in the chromatin.

Two studies of genetically manipulated mice by Bassing et al. and Celeste et al. reinforce previous evidence that H2AX is essential for genome stability and show further that even partial loss of the protein can accelerate tumorigenesis. Mice deficient in H2AX and the tumor suppressor protein p53 were found to develop tumors earlier and at a higher rate than did mice deficient in p53 alone, and these tumors were characterized by frequent chromosomal rearrangements. Thus, this histone can no longer be regarded solely as a structural component of chromatin, and researchers face the challenge of establishing precisely how it helps the cell keep its genome whole. — PAK

Cell 114, 359; 371 (2003).

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