Exons and introns exhibit transcriptional strand asymmetry of dinucleotide distribution, damage formation and DNA repair

Elisheva E. Heilbrun, May Merav, Sheera Adar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Recent cancer sequencing efforts have uncovered asymmetry in DNA damage induced mutagenesis between the transcribed and non-transcribed strands of genes. Here, we investigate the major type of damage induced by ultraviolet (UV) radiation, the cyclobutane pyrimidine dimers (CPDs), which are formed primarily in TT dinucleotides. We reveal that a transcriptional asymmetry already exists at the level of TT dinucleotide frequency and therefore also in CPD damage formation. This asymmetry is conserved in vertebrates and invertebrates and is completely reversed between introns and exons. We show the asymmetry in introns is linked to the transcription process itself, and is also found in enhancer elements. In contrast, the asymmetry in exons is not correlated to transcription, and is associated with codon usage preferences. Reanalysis of nucleotide excision repair, normalizing repair to the underlying TT frequencies, we show repair of CPDs is more efficient in exons compared to introns, contributing to the maintenance and integrity of coding regions. Our results highlight the importance of considering the primary sequence of the DNA in determining DNA damage sensitivity and mutagenic potential.

Original languageAmerican English
Article numberlqab020
JournalNAR Genomics and Bioinformatics
Volume3
Issue number1
DOIs
StatePublished - 1 Mar 2021

Bibliographical note

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© 2021 The Author(s).

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