Title:What Makes Y Family Pols Potential Candidates for Molecular Targeted Therapies and Novel Biotechnological Applications
VOLUME: 14 ISSUE: 1
Author(s):A. Tomasso, G. Casari and G. Maga
Affiliation:Institute of Molecular Genetics, IGM-CNR, via Abbiategrasso 207, I-27100 Pavia, Italy.
Keywords:Cancer, DNA damage tolerance, spermatogenesis, translesion synthesis, Y family.
Abstract:Nature has evolved DNA polymerases (Pols) with different replication fidelity with the purpose of
maintaining and faithfully propagating the genetic information. Besides the four classical Pols (Pol α, δ, ε, γ),
mammalian cells contain at least twelve specialized Pols whose functions have been discovered recently and
are still not completely elucidated. Among them, Pols belonging to the Y family contribute to cell survival by
promoting DNA damage tolerance. They are primarily involved in the translesion synthesis (TLS) pathway,
incorporating dNTPs in an error-free or error-prone manner, depending on the nature of the DNA lesion. From
an evolutionary point of view, their high mutagenic potential seems to guarantee the proper flexibility of vital
importance for both adaptation to a changeable environment and evolution of the species. These Pols are
subjected to a complex network of regulation, since their uncontrolled access to DNA might promote
mutagenesis and neoplastic transformation. Altered expression of Y family is a hallmark of several tumor
types. In recent years, the unique structure and properties of Y family Pols have been exploited to design
molecules that selectively interfere with the Pol of interest with minimal effect on normal cells. In addition, their
distinctive properties have been applied to innovative techniques, such as compartmentalized self-replication
(CSR), short-patch CSR, phage display and molecular breeding. These approaches are based on mutant Pols
provided with novel and ameliorated features and find applications in various fields, from biotechnology to
diagnostics, paleontology and forensic analysis.
