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Trends Genet. 2014 Jun;30(6):245-53. doi: 10.1016/j.tig.2014.03.005. Epub 2014 May 1.

Mechanisms of genome instability induced by RNA-processing defects.

Author information

1
Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada.
2
Michael Smith Laboratories, University of British Columbia, Vancouver, V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3, Canada.
3
Department of Medical Genetics, University of British Columbia, Vancouver, V6T 1Z3, Canada; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada. Electronic address: pstirling@bccrc.ca.

Abstract

The role of normal transcription and RNA processing in maintaining genome integrity is becoming increasingly appreciated in organisms ranging from bacteria to humans. Several mutations in RNA biogenesis factors have been implicated in human cancers, but the mechanisms and potential connections to tumor genome instability are not clear. Here, we discuss how RNA-processing defects could destabilize genomes through mutagenic R-loop structures and by altering expression of genes required for genome stability. A compelling body of evidence now suggests that researchers should be directly testing these mechanisms in models of human cancer.

KEYWORDS:

R-loops; RNA processing; cancer; genome instability; transcriptome

PMID:
24794811
PMCID:
PMC4039741
DOI:
10.1016/j.tig.2014.03.005
[Indexed for MEDLINE]
Free PMC Article

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