Radiation-induced chromosome aberrations: Insights gained from biophysical modeling

Lynn Hlatky, Rainer K. Sachs, Mariel Vazquez, Michael Cornforth

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Enzymatic misrepair of ionizing-radiation-induced DNA damage can produce large-scale rearrangements of the genome, such as translocations and dicentrics. These and other chromosome exchange aberrations can cause major phenotypic alterations, including cell death, mutation and neoplasia. Exchange formation requires that two (or more) genomic loci come together spatially. Consequently, the surprisingly rich aberration spectra uncovered by recently developed techniques, when combined with biophysically based computer modeling, help characterize large-scale chromatin architecture in the interphase nucleus. Most results are consistent with a picture whereby chromosomes are mainly confined to territories, chromatin motion is limited, and interchromosomal interactions involve mainly territory surfaces. Aberration spectra and modeling also help characterize DNA repair/misrepair mechanisms. Quantitative results for mammalian cells are best described by a breakage-and-reunion model, suggesting that the dominant recombinational mechanism during the G 0/G 1 phase of the cell cycle is non-homologous end-joining of radiogenic DNA double strand breaks. In turn, better mechanistic and quantitative understanding of aberration formation gives new insights into health-related applications.

Original languageEnglish (US)
Pages (from-to)714-723
Number of pages10
JournalBioEssays
Volume24
Issue number8
DOIs
StatePublished - 2002

Fingerprint

chromosome aberrations
Chromosomes
Aberrations
Chromosome Aberrations
Chromatin
DNA End-Joining Repair
Reunion
Radiation
chromatin
Interphase
Ionizing Radiation
DNA Repair
DNA Damage
chromosomes
DNA
Cell Cycle
Cell Death
Cells
Genome
DNA repair

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Biochemistry
  • Cell Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Agricultural and Biological Sciences (miscellaneous)
  • Plant Science

Cite this

Radiation-induced chromosome aberrations : Insights gained from biophysical modeling. / Hlatky, Lynn; Sachs, Rainer K.; Vazquez, Mariel; Cornforth, Michael.

In: BioEssays, Vol. 24, No. 8, 2002, p. 714-723.

Research output: Contribution to journalArticle

Hlatky, Lynn ; Sachs, Rainer K. ; Vazquez, Mariel ; Cornforth, Michael. / Radiation-induced chromosome aberrations : Insights gained from biophysical modeling. In: BioEssays. 2002 ; Vol. 24, No. 8. pp. 714-723.
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