Yeast DNA polymerase zeta (zeta) is essential for error-free replication past thymine glycol.
DNA polymerase zeta (Polzeta) promotes the mutagenic bypass of DNA lesions in eukaryotes. Genetic studies in Saccharomyces cerevisiae have indicated that relative to the contribution of other pathways, Polzeta makes only a modest contribution to lesion bypass. Intriguingly, however, disruption of the REV3 gene, which encodes the catalytic subunit of Polzeta, causes early embryonic lethality in mice. Here, we present genetic and biochemical evidence for the requirement of yeast Polzeta for predominantly error-free replication past thymine glycol (Tg), a DNA lesion formed frequently by free radical attack. These results raise the possibility that, as in yeast, in higher eukaryotes also, Polzeta makes a major contribution to the replicative bypass of Tgs as well as other lesions that block synthesis by replicative DNA polymerases. Such a preeminent role of Polzeta in lesion bypass would ensure that rapid cell divisions continue unabated during early embryonic development, thereby minimizing the generation of DNA strand breaks, chromosome aberrations, and the ensuing apoptotic response.
Johnson
Robert E
RE
Sealy Center for Molecular Science, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1061, USA.
Yu
Sung-Lim
SL
Prakash
Satya
S
Prakash
Louise
L
D020029:Base Pairing; D004249:DNA Damage; D004258:DNA Polymerase III / Q000502:physiology; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology; D005609:Free Radicals; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry*; D000099270:Y-Family DNA Polymerases
D004258:DNA Polymerase III; D004271:DNA, Fungal; D004259:DNA-Directed DNA Polymerase; D005609:Free Radicals; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D013941:Thymine; C029389:thymine glycol; C092602:REV3 protein, S cerevisiae; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases