Converging Checkpoint Signals

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Science  31 May 2002:
Vol. 296, Issue 5573, pp. 1573
DOI: 10.1126/science.296.5573.1573b

Eukaryotic cells are under continual assault by a wide variety of DNA-damaging agents. Cells cope with DNA damage by activating checkpoint pathways that delay cell cycle progression until the damage can be repaired. Identifying the molecular players in these checkpoint pathways and their interactions is a major goal of current cancer research.

Taniguchi et al. approach this problem by characterizing the phenotype of cells from patients with two inherited diseases that predispose to cancer, Fanconi anemia (FA) and ataxia telangiectasia (AT). Although they share some clinical signs, these diseases are thought to reflect distinct deficiencies in repair: FA cells are sensitive to DNA cross-linking agents, whereas AT cells are sensitive to ionizing radiation. Studying cells from a rare subtype of FA (D2) that shows heightened sensitivity to both forms of DNA damage, the authors find that the protein FANCD2, which is ubiquitinated in response to DNA cross-linking agents, is phosphorylated by the AT protein kinase ATM in response to ionizing radiation and as a prelude to activation of a damage checkpoint. — PAK

Cell109, 459 (2002).

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