Transcription-associated events affecting genomic integrity

Robin Sebastian; Philipp Oberdoerffer

doi:10.1098/rstb.2016.0288

Transcription-associated events affecting genomic integrity

Philos Trans R Soc Lond B Biol Sci. 2017 Oct 5;372(1731):20160288. doi: 10.1098/rstb.2016.0288.

Authors

Robin Sebastian¹, Philipp Oberdoerffer²

Affiliations

¹ Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Building 41, Room B907, Bethesda, MD 20892, USA.
² Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Building 41, Room B907, Bethesda, MD 20892, USA philipp.oberdoerffer@nih.gov.

Abstract

Accurate maintenance of genomic as well as epigenomic integrity is critical for proper cell and organ function. Continuous exposure to DNA damage is, thus, often associated with malignant transformation and degenerative diseases. A significant, chronic threat to genome integrity lies in the process of transcription, which can result in the formation of potentially harmful RNA : DNA hybrid structures (R-loops) and has been linked to DNA damage accumulation as well as dynamic chromatin reorganization. In sharp contrast, recent evidence suggests that active transcription, the resulting transcripts as well as R-loop formation can play multi-faceted roles in maintaining and restoring genome integrity. Here, we will discuss the emerging contributions of transcription as both a source of DNA damage and a mediator of DNA repair. We propose that both aspects have significant implications for genome maintenance, and will speculate on possible long-term consequences for the epigenetic integrity of transcribing cells.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.

Keywords: DSB repair; R-loop; chromatin; non-coding RNA; transcription.

Publication types

Review

MeSH terms

DNA Damage*
DNA Repair*
Epigenesis, Genetic*
Genome*
Transcription, Genetic*