DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes

Author(s)

Andrade-Lima, Leonardo C. ^{[1, 2, 3]} ; Veloso, Artur ^{[2, 3, 4]} ; Paulsen, Michelle T. ^{[2, 3]} ; Menck, Carlos F. M. ^[1] ; Ljungman, Mats ^{[2, 3, 5]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[2] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 - USA

^[3] Univ Michigan, Translat Oncol Program, Ann Arbor, MI 48109 - USA

^[4] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 - USA

^[5] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 - USA

• Document type: Journal article
• Source: Nucleic Acids Research; v. 43, n. 5, p. 2744-2756, MAR 11 2015.
• Web of Science Citations: 26

Abstract

The kinetics of DNA repair and RNA synthesis recovery in human cells following UV-irradiation were assessed using nascent RNA Bru-seq and quantitative long PCR. It was found that UV light inhibited transcription elongation and that recovery of RNA synthesis occurred as a wave in the 5'-3' direction with slow recovery and TC-NER at the 3' end of long genes. RNA synthesis resumed fully at the 3'-end of genes after a 24 h recovery in wild-type fibroblasts, but not in cells deficient in transcription-coupled nucleotide excision repair (TC-NER) or global genomic NER (GG-NER). Different transcription recovery profiles were found for individual genes but these differences did not fully correlate to differences in DNA repair of these genes. Our study gives the first genomewide view of how UV-induced lesions affect transcription and how the recovery of RNA synthesis of large genes are particularly delayed by the apparent lack of resumption of transcription by arrested polymerases. (AU)

• FAPESP's process: 09/52417-7 - Cell responses to genome damage
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants