The tail that wags the dog: p12, the smallest subunit of DNA polymerase ?, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.

ABSTRACT: DNA polymerase ? (Pol ?) is a key enzyme in eukaryotic DNA replication. Human Pol ? is a heterotetramer whose p12 subunit is degraded in response to DNA damage, leading to the in vivo conversion of Pol ?4 to Pol ?3. Two E3 ubiquitin ligases, RNF8 and CRL4(Cdt2), participate in the DNA damage-induced degradation of p12. We discuss how these E3 ligases integrate the formation of Pol ?3 and ubiquitinated PCNA for DNA repair processes. CRL4(Cdt2) partially degrades p12 during normal cell cycle progression, thereby generating Pol ?3 during S phase. This novel finding extends the current view of the role of Pol ?3 in DNA repair and leads to the hypothesis that it participates in DNA replication. The coordinated regulation of licensing factors and Pol ?3 by CRL4(Cdt2) now opens new avenues for control of DNA replication. A parallel study of Pol ?4 and Pol ?3 in Okazaki fragment processing provides evidence for a role of Pol ?3 in DNA replication. We discuss several new perspectives of the role of the 2 forms of Pol ? in DNA replication and repair, as well the significance of the integration of p12 regulation in DNA repair and cell cycle progression.

SUBMITTER: Lee MY 

PROVIDER: S-EPMC3925730 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature