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Concept of DNA Lesion Longevity and Chromosomal Translocations

Author:
Pannunzio, Nicholas R., Lieber, Michael R.
Source:
Trends in biochemical sciences 2018 v.43 no.7 pp. 490-498
ISSN:
0968-0004
Subject:
B-lymphocytes, DNA damage, chromosome translocation, cytidine deaminase, longevity, nucleotide sequences, patients, reactive oxygen species, single-stranded DNA, topology
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.
Agid:
5975717