The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage and genome instability

Accurate DNA replication and DNA repair are crucial for the maintenance of genome stability, and it is generally accepted that failure of these processes is a major source of DNA damage in cells. Intriguingly, recent evidence suggests that DNA damage is more likely to occur at genomic loci with high...

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Veröffentlicht in:	DNA repair Jg. 19; S. 84 - 94
Hauptverfasser:	Hamperl, Stephan, Cimprich, Karlene A.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Netherlands Elsevier B.V 01.07.2014
Schlagworte:	Activation-induced deaminase (AID) APOBEC family ASF splicing factor DNA - chemistry DNA - genetics DNA Breaks, Double-Stranded DNA Damage - genetics DNA Replication - genetics Double-strand breaks G-quadruplex Genome instability Genomic Instability - genetics Humans mRNP biogenesis Nucleic Acid Conformation R-loops RNA - chemistry RNA - genetics RNA processing factors RNA:DNA helicases RNase H Saccharomyces cerevisiae Senataxin THO/TREX complex THSC/TREX-2 Topoisomerase Transcription, Genetic Transcription–replication conflicts Senataxin TAM TAR THO/TREX complex ChIP SSB(s) THSC/TREX-2 Double-strand breaks CFS Transcription–replication conflicts RNP APOBEC AID mRNP biogenesis ssDNA Activation-induced deaminase (AID) RNAP(s) CSR G-quadruplex Genome instability CIN ASF splicing factor APOBEC family rDNA DSB(s) CTD RNA processing factors Topoisomerase RNase H R-loops RNA:DNA helicases
ISSN:	1568-7864, 1568-7856, 1568-7856
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Zusammenfassung:	Accurate DNA replication and DNA repair are crucial for the maintenance of genome stability, and it is generally accepted that failure of these processes is a major source of DNA damage in cells. Intriguingly, recent evidence suggests that DNA damage is more likely to occur at genomic loci with high transcriptional activity. Furthermore, loss of certain RNA processing factors in eukaryotic cells is associated with increased formation of co-transcriptional RNA:DNA hybrid structures known as R-loops, resulting in double-strand breaks (DSBs) and DNA damage. However, the molecular mechanisms by which R-loop structures ultimately lead to DNA breaks and genome instability is not well understood. In this review, we summarize the current knowledge about the formation, recognition and processing of RNA:DNA hybrids, and discuss possible mechanisms by which these structures contribute to DNA damage and genome instability in the cell.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	1568-7864 1568-7856 1568-7856
DOI:	10.1016/j.dnarep.2014.03.023