Novel conserved motifs in Rev1 C-terminus are required for mutagenic DNA damage tolerance.
The genes encoding Rev1 and DNA polymerase zeta (Rev3/Rev7) are together required for the vast majority of DNA damage-induced mutations in eukaryotes from yeast to humans. Here, we provide insight into the critical role that the Saccharomyces cerevisiae Rev1 C-terminus plays in the process of mutagenic DNA damage tolerance. The Rev1 C-terminus was previously thought to be poorly conserved and therefore not likely to be important for mediating protein-protein interactions. However, through comprehensive alignments of the Rev1 C-terminus, we have identified novel and hitherto unrecognized conserved motifs that we show play an essential role in REV1-dependent survival and mutagenesis in S. cerevisiae, likely in its post-replicative gap-filling mode. We further show that the minimal C-terminal fragment of Rev1 containing these highly conserved motifs is sufficient to interact with Rev7.
D'Souza
Sanjay
S
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Waters
Lauren S
LS
Walker
Graham C
GC
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002453:Cell Cycle; D002470:Cell Survival; D017124:Conserved Sequence; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D009713:Nucleotidyltransferases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000502:physiology; D016415:Sequence Alignment; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D009713:Nucleotidyltransferases; D029701:Saccharomyces cerevisiae Proteins; C092219:REV7 protein, S cerevisiae; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases