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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Bibliographic Details
Published in:DNA repair Vol. 19; pp. 84 - 94
Main Authors: Hamperl, Stephan, Cimprich, Karlene A.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.07.2014
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1568-7864
1568-7856
1568-7856
DOI:10.1016/j.dnarep.2014.03.023