期刊
EFFECTS OF GENOME STRUCTURE AND SEQUENCE ON VARIATION AND EVOLUTION
卷 1267, 期 -, 页码 24-30出版社
BLACKWELL SCIENCE PUBL
DOI: 10.1111/j.1749-6632.2012.06592.x
关键词
fragile site; FRA3B; flexibility peak; mitotic crossover; loss of heterozygosity; cancer
资金
- NIGMS NIH HHS [R15 GM093929, R15GM093929.] Funding Source: Medline
Certain chromosomal regions called common fragile sites are prone to difficulty during replication. Many tumors have been shown to contain alterations at fragile sites. Several models have been proposed to explain why these sites are unstable. Here we describe work to investigate models of fragile site instability using a yeast artificial chromosome carrying human DNA from a common fragile site region. In addition, we describe a yeast system to investigate whether repair of breaks at a naturally occurring fragile site in yeast, FS2, involves mitotic recombination between homologous chromosomes, leading to loss of heterozygosity (LOH). Our initial evidence is that repair of yeast fragile site breaks does lead to LOH, suggesting that human fragile site breaks may similarly contribute to LOH in cancer. This work is focused on gaining understanding that may enable us to predict and prevent the situations and environments that promote genetic changes that contribute to tumor progression.
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