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

Concept of DNA Lesion Longevity and Chromosomal Translocations.

Author information

1
University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
2
University of Southern California Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; Department of Pathology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA; Department of Molecular Microbiology and Immunology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA; Department of Biochemistry and Molecular Biology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA; Section of Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: lieber@usc.edu.

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.

PMID:
29735400
PMCID:
PMC6014902
DOI:
10.1016/j.tibs.2018.04.004
[Indexed for MEDLINE]
Free PMC Article

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