DNA polymerase eta (Pol η), is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''POLH''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
DNA polymerase eta is a eukaryotic
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
involved in the
DNA repair by translesion synthesis. The gene encoding DNA polymerase eta is
POLH, also known as XPV, because loss of this gene results in the disease
xeroderma pigmentosum. Polymerase eta is particularly important for allowing accurate translesion synthesis of DNA damage resulting from ultraviolet radiation or UV.
Function
This gene encodes a member of the Y family of specialized
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
s. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when
thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in
hypermutation during immunoglobulin class switch recombination.
Bypass of 8-oxoguanine
During DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inherita ...
of the ''Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
'' chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
, the oxidative DNA damage
DNA oxidation is the process of oxidative damage of deoxyribonucleic acid. As described in detail by Burrows et al., 8-oxo-2'-deoxyguanosine (8-oxo-dG) is the most common oxidative lesion observed in duplex DNA because guanine has a lower one-e ...
8-oxoguanine triggers a switch to translesion synthesis by DNA polymerase eta. This polymerase replicates 8-oxoguanine with an accuracy (insertion of a cytosine
Cytosine () (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached ...
opposite the 8-oxoguanine) of approximately 94%. Replication of 8-oxoguanine in the absence of DNA polymerase eta is less than 40%.
Clinical significance
Mutations in this gene result in XPV, a variant type of xeroderma pigmentosum, characterized by sun sensitivity, elevated incidence of skin cancer, and at the cellular level, by delayed replication and hypermutability after UV-irradiation
Interactions
POLH has been shown to interact with PCNA.
References
Further reading
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External links
GeneReviews/NIH/NCBI/UW entry on Xeroderma Pigmentosum
{{NLM content
DNA replication
DNA-binding proteins