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

PLoS One. 2015 Mar 10;10(3):e0118886. doi: 10.1371/journal.pone.0118886. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cells, Cultured
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism*
  • DNA Damage
  • Female
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Karyotype
  • Lymphocytes / drug effects
  • Lymphocytes / radiation effects
  • Lymphocytes / ultrastructure*
  • Male
  • Mitotic Index
  • Ultraviolet Rays*
  • Young Adult

Substances

  • Hydrogen Peroxide

Grant support

This study was funded in part by a Department of Defense grant “Mass Scale Biosensor Threat Diagnostic for In-Theater Defense Utilization” W81XWh-10-1-0732 for the assessment of chromosomal aberrations following genotoxicity exposure, and supported the following authors DI, LK, JLS and HGT. The authors would also like to acknowledge the financial support for the chromosome territory organization studies provided by the Herbert Wertheim College of Medicine at Florida International University (startup funds awarded to HGT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.