Sen1p Contributes to Genomic Integrity by Regulating Expression of Ribonucleotide Reductase 1 (<i>RNR1</i>) in <i>Saccharomyces cerevisiae</i>

<div><p>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 <i>RNR1</i> 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 <i>RNR1</i> gene and showed enhanced sensitivity to various DNA damaging agents. Moreover, <i>SEN1</i> mutants [Sen1-1 (G1747D), Sen1-2 (Δ1-975)] exhibited defects in DNA damage checkpoint activation. Surprisingly, <i>CRT1</i> 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 <i>RNR1.</i> Thus, the misregulation of Sen1p regulated genes can cause genomic instability that may lead to neurological disorders and premature aging.</p>