title: Diverse roles of RNA polymerase II-associated factor 1 complex in different subpathways of nucleotide excision repair.
abstract: Transcription-coupled repair (TCR) and global genomic repair (GGR) are two pathways of nucleotide excision repair (NER). In Saccharomyces cerevisiae, Rad26 is important but not absolutely required for TCR. Rpb4, a nonessential RNA polymerase II (Pol II) subunit that forms a subcomplex with Rpb7, and the Spt4-Spt5 complex, a transcription elongation factor, have been shown to suppress Rad26-independent TCR. The Pol II-associated factor 1 complex (Paf1C) has been shown to function in transcription elongation, 3'-processing of mRNAs, and posttranslational modification of histones. Here we show that Paf1C plays a marginal role in facilitating Rad26-dependent TCR but significantly suppresses Rad26-independent TCR. The suppression of Rad26-independent TCR is achieved by cooperating with Spt4-Spt5. We propose a model that, in the absence of Rad26, a lesion is "locked" in the active center of a Pol II elongation complex, which is stabilized by the coordinated interactions of Rpb4-Rpb7, Spt4-Spt5, and Paf1C with each other and with the core Pol II. We also found that Paf1C facilitates GGR, especially in internucleosomal linker regions. The facilitation of GGR is achieved through enabling monoubiquitination of histone H2B lysine 123 by Bre1, which in turn permits di- and trimethylation of histone H3 lysine 79 by Dot1. To our best knowledge, among the NER-modulating factors documented so far, Paf1C appears to have the most diverse functions in different NER pathways or subpathways.
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803.
authors: Danielle
authors: D
authors: Tatum
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803.
authors: Wentao
authors: W
authors: Li
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803.
authors: Margaret
authors: M
authors: Placer
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803. Electronic address: shli@vetmed.lsu.edu.
authors: Shisheng
authors: S
authors: Li
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D004260:DNA Repair; D015966:Gene Expression Regulation, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D006657:Histones; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D012319:RNA Polymerase II; C423309:RPB4 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C465758:RAD26 protein, S cerevisiae; D008239:Lysine