Recent findings from J.K. Cullen and co-authors highlight research in cell biology
2007 NOV 20 -- A report, 'Break-induced loss of heterozygosity in fission yeast: dual roles for homologous recombination in promoting translocations and preventing de novo telomere addition,' is newly published data in Molecular and Cellular Biology. "Loss of heterozygosity (LOH), a causal event in tumorigenesis, frequently encompasses multiple genetic loci and whole chromosome arms. However, the mechanisms leading to such extensive LOH are poorly understood," scientists in Didcot, the United Kingdom report. "We investigated the mechanisms of DNA double-strand break (DSB)-induced extensive LOH by screening for auxotrophic marker loss approximately 25 kb distal to an HO endonuclease break site within a nonessential minichromosome in Schizosaccharomyces pombe. Extensive break-induced LOH was infrequent, resulting from large translocations through both allelic crossovers and break-induced replication. These events required the homologous recombination (HR) genes rad32(+), rad50(+), nbs1(+), rhp51(+), rad22(+), rhp55(+), rhp54(+), and mus81(+). Surprisingly, LOH was still observed in HR mutants, which resulted predominantly from de novo telomere addition at the break site. De novo telomere addition was most frequently observed in rad22Delta and rhp55Delta backgrounds, which disrupt HR following end resection. Further, levels of de novo telomere addition, while increased in ku70Delta rhp55Delta strains, were reduced in exo1Delta rhp55Delta and an rhp55Delta strain overexpressing rhp51. These findings support a model in which HR prevents de novo telomere addition at DSBs by competing for resected ends," wrote J.K. Cullen and colleagues, . The researchers concluded: "Together, these results suggest that the mechanisms of break-induced LOH may be predicted from the functional status of the HR machinery." Cullen and colleagues published their study in Molecular and Cellular Biology (Break-induced loss of heterozygosity in fission yeast: dual roles for homologous recombination in promoting translocations and preventing de novo telomere addition. Molecular and Cellular Biology, 2007;27(21):7745-57). For more information, contact J.K. Cullen, MRC Radiation Oncology and Biology Unit, Harwell, Didcot, Oxfordshire OX11 0RD, UK. Publisher contact information for the journal Molecular and Cellular Biology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA. Keywords: United Kingdom, Didcot, Cell Biology, Cellular. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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