2014
DOI: 10.1128/mcb.00960-13
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A Saccharomyces cerevisiae RNase H2 Interaction Network Functions To Suppress Genome Instability

Abstract: Errors during DNA replication are one likely cause of gross chromosomal rearrangements (GCRs). Here, we analyze the role of RNase H2, which functions to process Okazaki fragments, degrade transcription intermediates, and repair misincorporated ribonucleotides, in preventing genome instability. The results demonstrate that rnh203 mutations result in a weak mutator phenotype and cause growth defects and synergistic increases in GCR rates when combined with mutations affecting other DNA metabolism pathways, inclu… Show more

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Cited by 46 publications
(45 citation statements)
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References 103 publications
(170 reference statements)
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“…Although the phenotypic differential provided by this assay system is small, the highest rate of NAHR was measured in the rnh201D pol2-M644G strain, and chromosomal size polymorphisms other than the selected translocations were only detected in the rnh201D background. Together, these observations were consistent with earlier reports for a role of ribonucleotides in the generation of gross chromosomal rearrangements in yeast (Wahba et al 2011;Allen-Soltero et al 2014) and increased cytogenetic abnormalities in mammalian cells (Reijns et al 2012).…”
Section: Discussionsupporting
confidence: 93%
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“…Although the phenotypic differential provided by this assay system is small, the highest rate of NAHR was measured in the rnh201D pol2-M644G strain, and chromosomal size polymorphisms other than the selected translocations were only detected in the rnh201D background. Together, these observations were consistent with earlier reports for a role of ribonucleotides in the generation of gross chromosomal rearrangements in yeast (Wahba et al 2011;Allen-Soltero et al 2014) and increased cytogenetic abnormalities in mammalian cells (Reijns et al 2012).…”
Section: Discussionsupporting
confidence: 93%
“…Although the phenotypic differential provided by this assay system is small, the highest rate of NAHR was measured in the rnh201D pol2-M644G strain, and chromosomal size polymorphisms other than the selected translocations were only detected in the rnh201D background. Together, these observations were consistent with earlier reports for a role of ribonucleotides in the generation of gross chromosomal rearrangements in yeast (Wahba et al 2011;Allen-Soltero et al 2014) and increased cytogenetic abnormalities in mammalian cells (Reijns et al 2012).The recombinogenic effects associated with RNase H2 mutants may result from misprocessing of scattered ribonucleotides incorporated into DNA, misprocessing of R-loops, or a combination of these two defects. The observation that increased and decreased ribonucleotide incorporation by Pol e correlates with the LOH rate leads us to propose that much of the LOH observed here in RNase H2 mutants is triggered by ribonucleotides incorporated by Pol e during leading strand replication.…”
supporting
confidence: 92%
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“…Consistent with the idea that the slippage events in the dinucleotide reporter arise as a result of Top1 cleavage at rNMP residues, the rnh202D sgs1D slippage events were mostly eliminated by the top1D mutation, being reduced from 140-fold increase over wildtype to 8X increase. A synergistic interaction between sgs1D and rnh203D (which has another subunit of RNaseH2 deleted) on gross chromosome rearrangement (GCR) rates has been reported, 15 however in this published study the synergistic increase was independent of Top1.…”
Section: Effect Of the Sgs1d Mutation On Rnmp-induced Mutagenesiscontrasting
confidence: 49%