Editors' ChoiceCheckpoint Signaling

Keeping the Forks on the Road

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Science's STKE  30 Jul 2002:
Vol. 2002, Issue 143, pp. tw280-TW280
DOI: 10.1126/stke.2002.143.tw280

Any failure in the many steps of DNA replication can result in the loss of chromosome integrity through the introduction of double-stranded (ds) DNA breaks (see the Viewpoint by Carr). Two reports focus on replication fork progression. To determine how replication forks are monitored, Sogo et al. directly visualized the structure of replication forks in wild-type and checkpoint-defective yeast cells using electron microscopy. In wild-type cells, stalled replication forks expose short regions of single-stranded (ss) DNA. In checkpoint-defective cells, replication intermediates with long ssDNA regions and reversed forks are found, suggesting that dsDNA breaks arise through inappropriate processing of the backed-up forks. The ATR/ATM family of chromosome-bound signal transduction proteins, which includes Mec1 in yeast, senses damaged or aberrant DNA and then triggers cell-cycle arrest and repair. Cha and Kleckner show that, in the absence of Mec1, DNA breaks occur in specific regions of chromatin, christened replication slow zones. Thus, Mec1 plays a role in replication fork progression during normal S phase of the cell cycle.

A. M. Carr, Checking that replication breakdown is not terminal, Science 297, 557-558 (2002). [Abstract] [Full Text]

J. M. Sogo, M. Lopes, M. Foiani, Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects, Science 297, 599-602 (2002). [Abstract] [Full Text]

R. S. Cha, N. Kleckner, ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones, Science 297, 602-606 (2002). [Abstract][Full Text]

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