title: Spatial positioning of all 24 chromosomes in the lymphocytes of six subjects: evidence of reproducible positioning and spatial repositioning following DNA damage with hydrogen peroxide and ultraviolet B.
abstract: The higher-order organization of chromatin is well-established, with chromosomes occupying distinct positions within the interphase nucleus. Chromatin is susceptible to, and constantly assaulted by both endogenous and exogenous threats. However, the effects of DNA damage on the spatial topology of chromosomes are hitherto, poorly understood. This study investigates the organization of all 24 human chromosomes in lymphocytes from six individuals prior to- and following in-vitro exposure to genotoxic agents: hydrogen peroxide and ultraviolet B. This study is the first to report reproducible distinct hierarchical radial organization of chromosomes with little inter-individual differences between subjects. Perturbed nuclear organization was observed following genotoxic exposure for both agents; however a greater effect was observed for hydrogen peroxide including: 1) More peripheral radial organization; 2) Alterations in the global distribution of chromosomes; and 3) More events of chromosome repositioning (18 events involving 10 chromosomes vs. 11 events involving 9 chromosomes for hydrogen peroxide and ultraviolet B respectively). Evidence is provided of chromosome repositioning and altered nuclear organization following in-vitro exposure to genotoxic agents, with notable differences observed between the two investigated agents. Repositioning of chromosomes following genotoxicity involved recurrent chromosomes and is most likely part of the genomes inherent response to DNA damage. The variances in nuclear organization observed between the two agents likely reflects differences in mobility and/or decondensation of chromatin as a result of differences in the type of DNA damage induced, chromatin regions targeted, and DNA repair mechanisms.
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Ioannou
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Kandukuri
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors.forename: Ameer
authors.initials: A
authors.lastname: Quadri
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Becerra
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America; March of Dimes Foundation, White Plains, New York, United States of America.
authors.forename: Joe Leigh
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida, United States of America; Biomolecular Sciences Institute, Florida International University, Miami, Florida, United States of America.
authors.forename: Helen G
authors.initials: HG
authors.lastname: Tempest
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059785:Karyotype; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure*; D008297:Male; D008940:Mitotic Index; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D006861:Hydrogen Peroxide