Faculty Member John H.J. Petrini

The ability of cells to repair DNA damage is a critical function that, when disrupted, can lead to the development of cancer. A new study by Memorial Sloan-Kettering investigators provides evidence that a form of molecular "velcro" -- known as the Rad50 hook -- holds broken strands of DNA together and stabilizes them during repair. The findings were published in the May issue of Nature Structural & Molecular Biology. [PubMed Abstract]

"Although previous work suggested that the hook was required for this process, this paper provided concrete evidence for Rad50's critical function during repair," explained molecular biologist John H.J. Petrini, the paper's senior author.

Rad50 is one of three proteins comprising the Mre11 protein complex, which is responsible for ensuring the integrity and stability of chromosomes and plays an important role in recognizing and repairing DNA damage. Using a series of genetic experiments in yeast cells, investigators created Rad50 mutants lacking the hook element. Without the Rad50 hook, mutant cells were unable to repair DNA properly. Conversely, insertion of a surrogate hook restored DNA repair functions.

The findings confirm the necessity of the Rad50 hook in DNA repair and give additional insight into how the Mre11 protein complex contributes to disease. Future work will concentrate on applying the same strategy in mammalian models.

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