Title:Multiple Forms of Human DNA Polymerase Delta Sub-Assembling in Cellular DNA Transactions
Volume: 17
Issue: 8
Author(s): Qian Zhang, Qian Zhang, Huiqing Chen, Yan Chen and Yajing Zhou
Affiliation:
Keywords:
DNA polymerase δ, heterotrimer Pol δ3, DNA replication, DNA damage and repair, p12 degradation, apoptosis.
Abstract: Among three major replicative DNA polymerases of the B-family, Pol α, Pol δ and Pol ε,
Pol δ plays an essential role in chromosomal DNA replication and is also involved in various DNA repair
processes in eukaryotes. Human Pol δ is commonly viewed as a heterotetrameric complex, consisting
of the catalytic subunit p125 and second subunit p50, together with two additional accessory
subunits, p68 and p12. A growing body of research has shown that the latter subunits play a critical
role in the regulation of Pol δ functions. The formation of a new form of Pol δ, heterotrimer Pol δ3, is
found by virtue of the depletion of p12 through the ubiquitin–proteasome pathway in response to DNA
damages that are trigged by UV irradiation, alkylating agents, oxidative and replication stresses. Pol δ3 exhibits significant
differences in properties to its progenitor with a major impact on cellular processes in genomic surveillance, DNA
replication and DNA repair. Our recent studies indicate that there exists an alternative pathway for Pol δ3 formation by
calpain-mediated proteolysis of p12 in a calcium-triggered apoptosis in living cells. In this article, we review and discuss
the recent advances from our group and others in the studies of human Pol δ with an emphasis on the generation of its
multiple forms by reconstitution and subsequent alternations in enzymatic properties, the multiple pathways of the Pol δ3
formation in living cells, and the phylogenetic analysis of the evolutionary history on POLD4 gene that is for the p12
subunit.
