Abstract：
:Genome instability, a hallmark of cancer progression, is thought to arise through DNA double strand breaks (DSBs). Studies in yeast and mammalian cells have shown that DSBs and instability can occur through RNA:DNA hybrids generated by defects in RNA elongation and splicing. We report that in yeast hybrids naturally form at many loci in wild-type cells, likely due to transcriptional errors, but are removed by two evolutionarily conserved RNase H enzymes. Mutants defective in transcriptional repression, RNA export and RNA degradation show increased hybrid formation and associated genome instability. One mutant, sin3Δ, changes the genome profile of hybrids, enhancing formation at ribosomal DNA. Hybrids likely induce damage in G1, S and G2/M as assayed by Rad52 foci. In summary, RNA:DNA hybrids are a potent source for changing genome structure. By preventing their formation and accumulation, multiple RNA biogenesis factors and RNase H act as guardians of the genome.
journal_name
Mol Celljournal_title
Molecular cellauthors
Wahba L,Amon JD,Koshland D,Vuica-Ross Mdoi
10.1016/j.molcel.2011.10.017subject
Has Abstractpub_date
2011-12-23 00:00:00pages
978-88issue
6eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00893-8journal_volume
44pub_type
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