RNH201

Summary

Gene Symbol: RNH201
Description: ribonuclease H2 catalytic subunit RNH201
Alias: RNH35, ribonuclease H2 catalytic subunit RNH201
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Chon H, Sparks J, Rychlik M, Nowotny M, Burgers P, Crouch R, et al. RNase H2 roles in genome integrity revealed by unlinking its activities. Nucleic Acids Res. 2013;41:3130-43 pubmed publisher
    ..This mutant definitively correlates the 2-5 bp deletions observed in rnh201? strains with single rNMPs in DNA...
  2. Wahba L, Amon J, Koshland D, Vuica Ross M. RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell. 2011;44:978-88 pubmed publisher
    ..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. ..
  3. Lazzaro F, Novarina D, Amara F, Watt D, Stone J, Costanzo V, et al. RNase H and postreplication repair protect cells from ribonucleotides incorporated in DNA. Mol Cell. 2012;45:99-110 pubmed publisher
  4. Jeong H, Backlund P, CHEN H, Karavanov A, Crouch R. RNase H2 of Saccharomyces cerevisiae is a complex of three proteins. Nucleic Acids Res. 2004;32:407-14 pubmed
    ..The multisubunit nature of S.cerevisiae RNase H2 may be important both for structural purposes and to provide a means of interacting with other proteins involved in DNA replication/repair and transcription. ..
  5. Sparks J, Chon H, Cerritelli S, Kunkel T, Johansson E, Crouch R, et al. RNase H2-initiated ribonucleotide excision repair. Mol Cell. 2012;47:980-6 pubmed publisher
    ..We observed partial redundancy for several of the enzymes in this pathway. Exo1 substitutes for FEN1 and Pol ε for Pol δ with reasonable efficiency. However, RNase H1 fails to substitute for RNase H2 in the incision step of RER. ..
  6. Williams J, Clausen A, Nick McElhinny S, Watts B, Johansson E, Kunkel T. Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase É›. DNA Repair (Amst). 2012;11:649-56 pubmed publisher
    ..Previous studies show that failure to repair ribonucleotides in the genome of rnh201Δ strains that lack RNase H2 activity elevates the rate of short deletions in tandem repeat sequences...
  7. Shen Y, Koh K, Weiss B, Storici F. Mispaired rNMPs in DNA are mutagenic and are targets of mismatch repair and RNases H. Nat Struct Mol Biol. 2011;19:98-104 pubmed publisher
    ..In the absence of mismatch repair and RNases H, ribonucleotide-driven gene modification increased by a factor of 47 in yeast and 77,000 in E. coli. ..
  8. Qiu J, Qian Y, Frank P, Wintersberger U, Shen B. Saccharomyces cerevisiae RNase H(35) functions in RNA primer removal during lagging-strand DNA synthesis, most efficiently in cooperation with Rad27 nuclease. Mol Cell Biol. 1999;19:8361-71 pubmed
    ..Based on our findings, we suggest that three alternative RNA primer removal pathways of different efficiencies involve RNase H(35) and Rad27 nucleases in yeast. ..
  9. Huertas P, Aguilera A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell. 2003;12:711-21 pubmed
    ..These data support a model to explain the connection between recombination, transcription, and mRNA metabolism and provide a new perspective to understanding transcription-associated recombination. ..

More Information

Publications36

  1. Arana M, Kerns R, Wharey L, Gerrish K, Bushel P, Kunkel T. Transcriptional responses to loss of RNase H2 in Saccharomyces cerevisiae. DNA Repair (Amst). 2012;11:933-41 pubmed publisher
    We report here the transcriptional responses in Saccharomyces cerevisiae to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2. Deleting RNH201 alters RNA expression of 349 genes by ≥1.5-fold (q-value <0...
  2. El Hage A, French S, Beyer A, Tollervey D. Loss of Topoisomerase I leads to R-loop-mediated transcriptional blocks during ribosomal RNA synthesis. Genes Dev. 2010;24:1546-58 pubmed publisher
    ..We conclude that the loss of Top1 enhances inherent R-loop formation, particularly over the 5' region of the rDNA, imposing persistent transcription blocks when RNase H is limiting. ..
  3. Nick McElhinny S, Kumar D, Clark A, Watt D, Watts B, Lundström E, et al. Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol. 2010;6:774-81 pubmed publisher
    ..This hierarchy was recapitulated in vivo in yeast strains lacking RNase H2. Moreover, the pol2-M644G rnh201Δ strain progressed more slowly through S phase, had elevated dNTP pools and generated 2-5-base-pair deletions ..
  4. Clark A, Lujan S, Kissling G, Kunkel T. Mismatch repair-independent tandem repeat sequence instability resulting from ribonucleotide incorporation by DNA polymerase ε. DNA Repair (Amst). 2011;10:476-82 pubmed publisher
    ..encoding a mutator allele of Pol É› (pol2-M644G), failure to remove rNMPs from DNA due to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2, results in deletion of 2-5 base pairs in short repetitive ..
  5. Kim N, Huang S, Williams J, Li Y, Clark A, Cho J, et al. Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science. 2011;332:1561-4 pubmed publisher
    ..The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease. ..
  6. Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin D, Shimada Y, et al. The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair. Genes Cells. 2000;5:789-802 pubmed
  7. Conover H, Lujan S, Chapman M, Cornelio D, Sharif R, Williams J, et al. Stimulation of Chromosomal Rearrangements by Ribonucleotides. Genetics. 2015;201:951-61 pubmed publisher
    ..homologous recombination (NAHR) in mutant diploid strains with deletions of genes encoding RNase H2 subunits (rnh201Δ, rnh202Δ, and rnh203Δ), topoisomerase 1 (TOP1Δ), and/or carrying mutant alleles of DNA ..
  8. Lafuente Barquero J, Luke Glaser S, Graf M, Silva S, Gómez González B, Lockhart A, et al. The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage. PLoS Genet. 2017;13:e1007136 pubmed publisher
    ..The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids. ..
  9. Su X, Freudenreich C. Cytosine deamination and base excision repair cause R-loop-induced CAG repeat fragility and instability in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2017;114:E8392-E8401 pubmed publisher
    ..cytosine deaminase Fcy1 significantly decreased the rate of CAG repeat fragility and contractions in the rnh1?rnh201? background, indicating that Fcy1-mediated deamination is one cause of breakage and contractions in the ..
  10. El Hage A, Webb S, Kerr A, Tollervey D. Genome-wide distribution of RNA-DNA hybrids identifies RNase H targets in tRNA genes, retrotransposons and mitochondria. PLoS Genet. 2014;10:e1004716 pubmed publisher
    ..Finally, R-loops were detected on actively transcribed protein-coding genes in the wild-type, particularly over the second exon of spliced ribosomal protein genes. ..
  11. Tumbale P, Williams J, Schellenberg M, Kunkel T, Williams R. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature. 2014;506:111-5 pubmed publisher
    ..Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease. ..
  12. Graf M, Bonetti D, Lockhart A, Serhal K, Kellner V, Maicher A, et al. Telomere Length Determines TERRA and R-Loop Regulation through the Cell Cycle. Cell. 2017;170:72-85.e14 pubmed publisher
    ..Thus, the telomere length-dependent regulation of TERRA and TERRA R-loops is a critical determinant of the rate of replicative senescence. ..
  13. Cornelio D, Sedam H, Ferrarezi J, Sampaio N, Argueso J. Both R-loop removal and ribonucleotide excision repair activities of RNase H2 contribute substantially to chromosome stability. DNA Repair (Amst). 2017;52:110-114 pubmed publisher
    ..we measured rates of loss-of-heterozygosity (LOH) in diploid Saccharomyces cerevisiae yeast strains carrying the rnh201-RED separation-of-function allele, encoding a version of RNase H2 that is RER-defective, but partly retains its ..
  14. Yadav P, Owiti N, Kim N. The role of topoisomerase I in suppressing genome instability associated with a highly transcribed guanine-rich sequence is not restricted to preventing RNA:DNA hybrid accumulation. Nucleic Acids Res. 2016;44:718-29 pubmed publisher
    ..Together, our data provide a strong support for a function of Top1 in suppressing genome instability at the guanine-run containing sequence that goes beyond preventing the transcription-associated RNA:DNA hybrid formation. ..
  15. Keskin H, Shen Y, Huang F, Patel M, Yang T, Ashley K, et al. Transcript-RNA-templated DNA recombination and repair. Nature. 2014;515:436-9 pubmed publisher
    ..Thus, considering the abundance of RNA transcripts in cells, RNA may have a marked impact on genomic stability and plasticity. ..
  16. Williams J, Clausen A, Lujan S, Marjavaara L, Clark A, Burgers P, et al. Evidence that processing of ribonucleotides in DNA by topoisomerase 1 is leading-strand specific. Nat Struct Mol Biol. 2015;22:291-7 pubmed publisher
  17. Donigan K, Cerritelli S, McDonald J, Vaisman A, Crouch R, Woodgate R. Unlocking the steric gate of DNA polymerase η leads to increased genomic instability in Saccharomyces cerevisiae. DNA Repair (Amst). 2015;35:1-12 pubmed publisher
    ..The sensitivity is due, in part, to RNase H2 activity, as an isogenic rnh201Δ strain is roughly 50-fold more UV-resistant than its RNH201(+) counterpart...
  18. Nguyen T, Tak Y, Lee C, Kang Y, Cho I, Seo Y. Analysis of subunit assembly and function of the Saccharomyces cerevisiae RNase H2 complex. FEBS J. 2011;278:4927-42 pubmed publisher
    RNase H2 of Saccharomyces cerevisiae consists of three essential subunits (Rnh201, Rnh202 and Rnh203) and plays a critical role in the removal of RNA incorporated in duplex DNA...
  19. O Connell K, Jinks Robertson S, Petes T. Elevated Genome-Wide Instability in Yeast Mutants Lacking RNase H Activity. Genetics. 2015;201:963-75 pubmed publisher
    ..throughout the yeast genome in diploid strains of Saccharomyces cerevisiae lacking RNase H1 (rnh1Δ), RNase H2 (rnh201Δ), or both RNase H1 and RNase H2 (rnh1Δ rnh201Δ)...
  20. Cho J, Huang S, Burgers P, Shuman S, Pommier Y, Jinks Robertson S. Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo. Nucleic Acids Res. 2016;44:7714-21 pubmed publisher
    ..Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process. ..
  21. Abraham K, Chan J, Salvi J, Ho B, Hall A, Vidya E, et al. Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA-DNA hybrids. Nucleic Acids Res. 2016;44:8870-8884 pubmed
  22. Williams J, Gehle D, Kunkel T. The role of RNase H2 in processing ribonucleotides incorporated during DNA replication. DNA Repair (Amst). 2017;53:52-58 pubmed publisher
    ..activities in maintenance of genome stability, here we investigate the phenotypes of a mutant of yeast RNase H2 (rnh201-RED; ribonucleotide excision defective) that retains activity on RNA-DNA hybrids but is unable to cleave single ..
  23. Ghodgaonkar M, Lazzaro F, Olivera Pimentel M, Artola Borán M, Cejka P, Reijns M, et al. Ribonucleotides misincorporated into DNA act as strand-discrimination signals in eukaryotic mismatch repair. Mol Cell. 2013;50:323-32 pubmed publisher
    ..We therefore propose that ribonucleotides misincoporated during DNA replication serve as physiological markers of the nascent DNA strand. ..
  24. Williams J, Smith D, Marjavaara L, Lujan S, Chabes A, Kunkel T. Topoisomerase 1-mediated removal of ribonucleotides from nascent leading-strand DNA. Mol Cell. 2013;49:1010-5 pubmed publisher
  25. Huang S, Williams J, Arana M, Kunkel T, Pommier Y. Topoisomerase I-mediated cleavage at unrepaired ribonucleotides generates DNA double-strand breaks. EMBO J. 2017;36:361-373 pubmed publisher
    ..Taken together, these results define Top1 as a source of DSBs and genome instability when ribonucleotides incorporated by the replicative polymerases are not removed by RNase H2. ..
  26. Luke B, Panza A, Redon S, Iglesias N, Li Z, Lingner J. The Rat1p 5' to 3' exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell. 2008;32:465-77 pubmed publisher
    ..Thus, telomeric transcription combined with Rat1p-dependent TERRA degradation is important for regulating telomerase in yeast. Telomere transcription is conserved in different kingdoms of the eukaryotic domain. ..
  27. Frank P, Braunshofer Reiter C, Wintersberger U. Yeast RNase H(35) is the counterpart of the mammalian RNase HI, and is evolutionarily related to prokaryotic RNase HII. FEBS Lett. 1998;421:23-6 pubmed
    ..Deletion of the gene (called RNH35) from the yeast genome leads to an about 75% decrease of RNase H activity in preparations from the mutated, still ..