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Researchers at University of Oxford publish new data on cell biology
2009 AUG 4 - (NewsRx.com) -- According to a study from Oxford, the United Kingdom, "Several inherited syndromes in humans are associated with cancer predisposition. The gene products defective in two of these disorders, BLM ( a helicase defective in Bloom's syndrome)(1) and FANC A-N ( defective in Fanconi anaemia)(2), associate in a multienzyme complex called BRAFT(3)." "How these proteins suppress tumorigenesis remains unclear, although both conditions are associated with chromosome instability. Here we show that the Fanconi anaemia proteins FANCD2 and FANCI specifically associate with common fragile site loci irrespective of whether the chromosome is broken. Unexpectedly, these loci are frequently interlinked through BLM-associated ultra-fine DNA bridges(4) (UFBs) even as cells traverse mitosis. Similarly to fragile site expression(5), fragile site bridging is induced after partial inhibition of DNA replication. We propose that, after replication stress, sister chromatids are interlinked by replication intermediates primarily at genetic loci with intrinsic replication difficulties, such as fragile sites. In Bloom's syndrome cells, inefficient resolution of DNA linkages at fragile sites gives rise to increased numbers of anaphase UFBs and micronuclei containing fragile site DNA," wrote K.L. Chan and colleagues, University of Oxford. The researchers concluded: "Our data have general implications concerning the contribution of fragile site loci to chromosomal instability and tumorigenesis." Chan and colleagues published their study in Nature Cell Biology (Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nature Cell Biology, 2009;11(6):753-U120). For more information, contact I.D. Hickson, University of Oxford, John Radcliffe Hospital, Weatherall Institute Molecular Medical, Oxford OX3 9DS, UK. Publisher contact information for the journal Nature Cell Biology is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England. Keywords: United Kingdom, Oxford, Life Sciences, Cancer, Oncology, Enzyme Research, Helicase, DNA, Cell Biology, University of Oxford. This article was prepared by Science Letter editors from staff and other reports. Copyright 2009, Science Letter via NewsRx.com.
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