title: Sen1p contributes to genomic integrity by regulating expression of ribonucleotide reductase 1 (RNR1) in Saccharomyces cerevisiae.
abstract: Gene expression is a multi-step process which requires recruitment of several factors to promoters. One of the factors, Sen1p is an RNA/DNA helicase implicated in transcriptional termination and RNA processing in yeast. In the present study, we have identified a novel function of Sen1p that regulates the expression of ribonucleotide reductase RNR1 gene, which is essential for maintaining genomic integrity. Cells with mutation in the helicase domain or lacking N-terminal domain of Sen1p displayed a drastic decrease in the basal level transcription of RNR1 gene and showed enhanced sensitivity to various DNA damaging agents. Moreover, SEN1 mutants [Sen1-1 (G1747D), Sen1-2 (Δ1-975)] exhibited defects in DNA damage checkpoint activation. Surprisingly, CRT1 deletion in Sen1p mutants (Sen1-1, Sen1-2) was partly able to rescue the slow growth phenotype upon genotoxic stress. Altogether, our observations suggest that Sen1p is required for cell protection against DNA damage by regulating the expression of DNA repair gene RNR1. Thus, the misregulation of Sen1p regulated genes can cause genomic instability that may lead to neurological disorders and premature aging.
authors.affiliation: Laboratory of Chromatin Biology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal, India.
authors.forename: Upendarrao
authors.initials: U
authors.lastname: Golla
authors.forename: Vikash
authors.initials: V
authors.lastname: Singh
authors.forename: Gajendra Kumar
authors.initials: GK
authors.lastname: Azad
authors.forename: Prabhat
authors.initials: P
authors.lastname: Singh
authors.forename: Naveen
authors.initials: N
authors.lastname: Verma
authors.forename: Papita
authors.initials: P
authors.lastname: Mandal
authors.forename: Sakshi
authors.initials: S
authors.lastname: Chauhan
authors.forename: Raghuvir S
authors.initials: RS
authors.lastname: Tomar
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D042822:Genomic Instability; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D021381:Protein Transport; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics; D012264:Ribonucleotide Reductases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D009153:Mutagens; D047428:Protein Kinase Inhibitors; C114542:RFX1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C570014:RNR2 protein, S cerevisiae; D012264:Ribonucleotide Reductases; C551024:Rnr1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; C542347:SEN1 protein, S cerevisiae; D004265:DNA Helicases; D020365:RNA Helicases