Open AccessExons and introns exhibit transcriptional strand asymmetry of dinucleotide distribution, damage formation and DNA repair
Author(s) -
Elisheva E. Heilbrun,
May Merav,
Sheera Adar
Publication year - 2021
Publication title -
nar genomics and bioinformatics
Language(s) - English
Resource type - Journals
ISSN - 2631-9268
DOI - 10.1093/nargab/lqab020
Subject(s) - biology , intron , pyrimidine dimer , dna damage , exon , genetics , dna repair , dna , gene , nucleotide excision repair , transcription (linguistics) , mutagenesis , mutation , linguistics , philosophy
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.