Abstract
This short article summarizes some of the research carried out recently by my laboratory colleagues on the function of DNA polymerase zeta (polζ) in mammalian cells. Some personal background is also described, relevant to research associations with Yale University and its continuing influence. Polζ is involved in the bypass of many DNA lesions by translesion DNA synthesis and is responsible for the majority of DNA damage-induced point mutagenesis in mammalian cells (including human cells), as well as in yeast. We also found that the absence of this enzyme leads to gross chromosomal instability in mammalian cells and increased spontaneous tumorigenesis in mice. Recently, we discovered a further unexpectedly critical role for polζ: it plays an essential role in allowing continued rapid proliferation of cells and tissues. These observations and others indicate that polζ engages frequently during DNA replication to bypass and tolerate DNA lesions or unusual DNA structures that are barriers for the normal DNA replication machinery.
Original language | English (US) |
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Pages (from-to) | 507-516 |
Number of pages | 10 |
Journal | Yale Journal of Biology and Medicine |
Volume | 86 |
Issue number | 4 |
State | Published - Dec 2013 |
Keywords
- DNA damage
- DNA polymerase
- Mouse
- Pol zeta
- Ultraviolet radiation
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology