Concept of DNA Lesion Longevity and Chromosomal Translocations

Trends Biochem Sci. 2018 Jul;43(7):490-498. doi: 10.1016/j.tibs.2018.04.004. Epub 2018 May 4.

Abstract

A subset of chromosomal translocations related to B cell malignancy in human patients arises due to DNA breaks occurring within defined 20-600 base pair (bp) zones. Several factors influence the breakage rate at these sites including transcription, DNA sequence, and topological tension. These factors favor non-B DNA structures that permit formation of transient single-stranded DNA (ssDNA), making the DNA more vulnerable to agents such as the enzyme activation-induced cytidine deaminase (AID) and reactive oxygen species (ROS). Certain DNA lesions created during the ssDNA state persist after the DNA resumes its normal duplex structure. We propose that factors favoring both formation of transient ssDNA and persistent DNA lesions are key in determining the DNA breakage mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Chromosome Fragile Sites*
  • Cytidine Deaminase / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Breaks, Single-Stranded*
  • DNA, Single-Stranded / chemistry
  • DNA, Single-Stranded / metabolism
  • Humans
  • Kinetics
  • Leukemia, B-Cell / genetics*
  • Leukemia, B-Cell / metabolism
  • Models, Genetic*
  • Reactive Oxygen Species / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Species Specificity
  • Translocation, Genetic*

Substances

  • DNA, Single-Stranded
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase