Activation of Fanconi Anemia Pathway in Cells with Re-Replicated DNA

Wenge Zhu and Anindya Dutta

volume 5 | issue 20

15 october 2006
Pages: 2306 - 2309

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To maintain genome stability, the cell has to limit initiation of DNA replication to once per cell cycle. Loss of this control leads to DNA re-replication with repeated firing of replication origins in the same cell cycle. Re-replication generates both ssDNA and double strand breaks, as well as activation of the DNA damage checkpoint. In re-replicated cells, activation of the checkpoint is critical to arrest cells in G2 resulting in accumulation of cells with re-replicated DNA. Abrogation of this checkpoint suppresses the progressive accumulation of cells with excess DNA and causes apoptosis. Recently, the Fanconi Anemia pathway was reported to be activated in re-replicating cells. Interestingly, FA core complexes but not FANCD2, is required for checkpoint activation in re-replicated cells, suggesting that the pathway to checkpoint activation requires the ubiquitination of substrates other than FANCD2. In addition, FANCD2 is required for recruitment of Rad51 to foci in re-replicated cells, so that the repair pathways activated after small degrees of re-replication are expected to be compromised in cells with mutations in the FA pathway.

Authors

Wenge Zhu

n, University of Virginia School of Medicine, Charlottesville, VA

Anindya Dutta

University of Virginia School of Medicine Charlottesville

We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link: