Rpb4 and Rpb9 mediate subpathways of transcription-coupled DNA repair in Saccharomyces cerevisiae

Li, Shisheng; Smerdon, Michael J.

doi:10.1093/emboj/cdf589

Cited by 119 publications

(176 citation statements)

References 60 publications

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“…It is possible that Rpb4/7 recruits Ccr4-Not and other elongation factors to promote transcription. Likewise, both Ccr4-Not and Rpb4 have been implicated in transcription-coupled DNA repair (24,25), and this physical interaction may play an important role here, too. These possibilities remain to be tested.…”

Section: Discussionmentioning

confidence: 93%

The Rpb4/7 Module of RNA Polymerase II Is Required for Carbon Catabolite Repressor Protein 4-Negative on TATA (Ccr4-Not) Complex to Promote Elongation

Babbarwal

Reese

2014

Journal of Biological Chemistry

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Background: mRNA transcription and decay are coordinated processes. Results: The Rpb4/7 module of RNA polymerase II is required for the transcription and mRNA decay factor Ccr4-Not to associate with elongation complexes. Conclusion: Association between these two entities is required for Ccr4-Not to promote transcription elongation. Significance: Our work provides molecular insights into how transcription and mRNA decay are linked.

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Section: Discussionmentioning

confidence: 93%

The Rpb4/7 Module of RNA Polymerase II Is Required for Carbon Catabolite Repressor Protein 4-Negative on TATA (Ccr4-Not) Complex to Promote Elongation

Babbarwal

Reese

2014

Journal of Biological Chemistry

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“…The cells were incubated at 30°C in the dark to allow them to repair their DNA, and aliquots were collected at different time points. Genomic DNA was isolated from the cells as described previously (16).…”

Section: Methodsmentioning

confidence: 99%

“…(15) were kindly provided by Dr. Ali Shilatifard (Stowers Institute for Medical Research). DOT1 and RAD16 deletions were created using procedures described previously (16).…”

Section: Nucleotide Excision Repair (Ner)mentioning

confidence: 99%

Evidence That the Histone Methyltransferase Dot1 Mediates Global Genomic Repair by Methylating Histone H3 on Lysine 79

Tatum

2011

Journal of Biological Chemistry

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Global genomic repair (GGR) and transcription coupled repair (TCR) are two pathways of nucleotide excision repair (NER) that differ in the damage recognition step. How NER factors, especially GGR factors, access DNA damage in the chromatin of eukaryotic cells has been poorly understood. Dot1, a histone methyltransferase required for methylation of histone H3 lysine 79 (H3K79), has been shown to confer yeast cells with resistance to DNA-damaging agents and play a role in activation of DNA damage checkpoints. Here, we show that Dot1 and H3K79 methylation are required for GGR in both nucleosomal core regions and internucleosomal linker DNA, but play no role in TCR. H3K79 trimethylation contributes to but is not absolutely required for GGR, and lower levels of H3K79 methylation (mono-and dimethylation) also promote GGR. Our results also indicate that the roles of Dot1 and H3K79 methylation in GGR are not achieved by either activating DNA damage checkpoints or regulating the expression of the GGR-specific factor Rad16. Rather, the methylated H3K79 may serve as a docking site for the GGR machinery on the chromatin. Our studies identified a novel GGR-specific NER factor and unveiled the critical link between a covalent histone modification and GGR. Nucleotide excision repair (NER)2 is a highly conserved DNA repair mechanism that removes a wide variety of bulky, helixdistorting lesions that generally obstruct transcription and normal replication, such as UV-induced cyclobutane pyrimidine dimers (CPDs) (1). Transcription-coupled repair (TCR) is a specialized NER pathway that is dedicated to rapid repair in the transcribed strand (TS) of active genes and is believed to be initiated by an RNA polymerase stalled at a lesion in the TS (2). The genome-wide NER, which includes repair in the nontranscribed strand (NTS) of actively transcribed genes, is termed global genomic repair (GGR) to be distinguished from TCR. The two NER pathways share most of the common repair factors and differ only in the damage recognition step (1).In the budding yeast Saccharomyces cerevisiae, Rad7, Rad16, and Elc1 are specifically required for GGR (3, 4). The exact roles of these proteins in GGR are not yet clear. The Rad7-Rad16 complex may act as an ATP-dependent motor that translocates along the DNA in search of damage, and upon encountering a lesion, the complex is stalled, which may remodel and open damaged chromatin, thereby facilitating recruitment of other NER factors (5). Elc1 has been shown to be a component of a ubiquitin ligase that contains Rad7 and Rad16 (6). It has also been suggested that Elc1 is a component of another ubiquitin ligase complex, which contains Ela1, Cul3, and Roc1 but not Rad7 and Rad16 (7). The role of Elc1 in GGR does not seem to be subsidiary to that of Rad7 and Rad16 (3).The molecular basis of chromatin dynamics during NER in eukaryotic cells is still not well understood (8, 9). The basic repeating component of chromatin is the nucleosome, which comprises 146 bp of DNA wrapped around an octomer of the four core hi...

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“…To initiate TCR, the NER machinery can be recruited by two redundant mechanisms that are mediated by the Rpb9 subunit of RNA polymerase II or by Rad26 (Li and Smerdon 2002). Elimination of either Rad7 or Rad16 elevated the frequency of UV-induced sectored ade2 adeX colonies seven-to eight-fold, which was slightly, but significantly greater than the elevation observed in the complete absence of NER (P , 0.001).…”

Section: Ner Is Required For Two-strand Mutations In G0 Cellsmentioning

confidence: 96%

The Mechanism of Nucleotide Excision Repair-Mediated UV-Induced Mutagenesis in Nonproliferating Cells

Kozmin

Jinks-Robertson

2013

Genetics

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Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such two-strand mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colonycolor system was used to examine the genetic control of UV-induced mutagenesis in nondividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production of these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32, and Rad5) and in the early steps of the DNA-damage checkpoint response (Rad17, Mec3, Ddc1, Mec1, and Rad9) were required for the production of two-strand mutations. There was no involvement, however, for the Pol h translesion synthesis DNA polymerase, the Mms2-Ubc13 postreplication repair complex, downstream DNA-damage checkpoint factors (Rad53, Chk1, and Dun1), or the Exo1 exonuclease. Our data support models in which UV-induced mutagenesis in nondividing cells occurs during the Pol z-dependent filling of lesion-containing, NER-generated gaps. The requirement for specific DNA-damage checkpoint proteins suggests roles in recruiting and/or activating factors required to fill such gaps. MUTAGENESIS associated with induced DNA damage is generally considered to occur during S phase, when polymerase-blocking lesions are bypassed in an error-prone manner by a translesion synthesis (TLS) DNA polymerase. In the yeast Saccharomyces cerevisiae, ultraviolet (UV)-induced mutagenesis is dependent on Pol z (Rev3-Rev7) and Rev1, with rev1, rev3, or rev7 mutants exhibiting a "reversionless" phenotype in response to UV irradiation (Lawrence 2002). Just as induced mutagenesis is considered to be a consequence of error-prone TLS, nucleotide excision repair (NER) is thought to counteract such mutagenesis by removing UV-induced lesions before they can be encountered during DNA replication.Although NER is generally considered to be an error-free, mutation-avoidance mechanism, data obtained .30 years ago demonstrated a pro-mutation role of NER in the UVinduced mutagenesis that occurs in nondividing yeast cells (Eckardt and Haynes 1977;James and Kilbey 1977;James et al. 1978;Eckardt et al. 1980). Either the induction of recessive lethal mutations in diploid strains (James and Kilbey 1977;James et al. 1978) or the induction of forward mutations in the de novo adenine biosynthetic pathway in haploid strains was monitored (Eckardt and Haynes 1977;Eckardt et al. 1980). Despite the differences in assay systems used, the authors reached the same conclusions. First, UVinduced mutations in nondi...

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Rpb4 and Rpb9 mediate subpathways of transcription-coupled DNA repair in Saccharomyces cerevisiae

Cited by 119 publications

References 60 publications

The Rpb4/7 Module of RNA Polymerase II Is Required for Carbon Catabolite Repressor Protein 4-Negative on TATA (Ccr4-Not) Complex to Promote Elongation

The Rpb4/7 Module of RNA Polymerase II Is Required for Carbon Catabolite Repressor Protein 4-Negative on TATA (Ccr4-Not) Complex to Promote Elongation

Evidence That the Histone Methyltransferase Dot1 Mediates Global Genomic Repair by Methylating Histone H3 on Lysine 79

The Mechanism of Nucleotide Excision Repair-Mediated UV-Induced Mutagenesis in Nonproliferating Cells

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