The mutation of a novel Saccharomyces cerevisiae SRL4 gene rescues the lethality of rad53 and lcd1 mutations by modulating dNTP levels.
The SRL4 (YPL033C) gene was initially identified by the screening of Saccharomyces cerevisiae genes that play a role in DNA metabolism and/or genome stability using the SOS system of Escherichia coli. In this study, we found that the srl4Delta mutant cells were resistant to the chemicals that inhibit nucleotide metabolism and evidenced higher dNTP levels than were observed in the wild-type cells in the presence of hydroxyurea. The mutant cells also showed a significantly faster growth rate and higher dNTP levels at low temperature (16 degrees C) than were observed in the wild-type cells, whereas we detected no differences in the growth rate at 30 degrees C. Furthermore, srl4Delta was shown to suppress the lethality of mutations of the essential S phase checkpoint genes, RAD53 and LCD1. These results indicate that SRL4 may be involved in the regulation of dNTP production by its function as a negative regulator of ribonucleotide reductase.
Choi
Do-Hee
DH
Department of Biological Sciences, College of Natural Science, Inha University, Incheon 402-751, Republic of Korea.
Oh
Young-Mi
YM
Kwon
Sung-Hun
SH
Bae
Sung-Ho
SH
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D064447:Checkpoint Kinase 2; D003080:Cold Temperature; D004249:DNA Damage; D003854:Deoxyribonucleotides / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006918:Hydroxyurea / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003854:Deoxyribonucleotides; C440014:LCD1 protein, S cerevisiae; D019384:Nucleic Acid Synthesis Inhibitors; D010750:Phosphoproteins; C528779:SRL4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012264:Ribonucleotide Reductases; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D006918:Hydroxyurea