title: Sites of genetic instability in mitosis and cancer.
abstract: 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.
authors.affiliation: Department of Biology, Eastern Michigan University, Ypsilanti, Michigan, USA anne.casper@emich.edu
authors.forename: Anne M
authors.initials: AM
authors.lastname: Casper
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Rosen
authors.forename: Kaveri D
authors.initials: KD
authors.lastname: Rajula
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics; D056905:Chromosome Breakpoints; D043283:Chromosome Fragile Sites; D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics*; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D042822:Genomic Instability; D059765:Homologous Recombination; D006801:Humans; D019656:Loss of Heterozygosity; D008938:Mitosis; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D015003:Yeasts / Q000235:genetics / Q000502:physiology; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D004256:DNA Polymerase I; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C083536:POL1 protein, S cerevisiae