title: Sequence and structural basis for chromosomal fragility during translocations in cancer.
abstract: Chromosomal aberration is considered to be one of the major characteristic features in many cancers. Chromosomal translocation, one type of genomic abnormality, can lead to deregulation of critical genes involved in regulating important physiological functions such as cell proliferation and DNA repair. Although chromosomal translocations were thought to be random events, recent findings suggest that certain regions in the human genome are more susceptible to breakage than others. The possibility of deviation from the usual B-DNA conformation in such fragile regions has been an active area of investigation. This review summarizes the factors that contribute towards the fragility of these regions in the chromosomes, such as DNA sequences and the role of different forms of DNA structures. Proteins responsible for chromosomal fragility, and their mechanism of action are also discussed. The effect of positioning of chromosomes within the nucleus favoring chromosomal translocations and the role of repair mechanisms are also addressed.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002873:Chromosome Fragility; D004249:DNA Damage; D004260:DNA Repair; D042822:Genomic Instability; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D014178:Translocation, Genetic
chemical_list: D002843:Chromatin