DNA polymerase theta is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
that in humans is encoded by the ''POLQ''
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 ...
.
This polymerase plays a key role in one of the three major double strand break repair pathways: theta-mediated end joining (TMEJ). Most double-strand breaks are repaired by
non-homologous end joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direc ...
(NHEJ) or
homology directed repair (HDR). However, in some contexts, NHEJ and HR are insufficient and TMEJ is the only solution to repair the break. TMEJ is often described as alternative NHEJ, but differs in that it lacks a requirement for the
Ku heterodimer, and it can only act on resected DNA ends.
Following annealing of short (i.e., a few nucleotides) regions on the DNA overhangs, DNA polymerase theta catalyzes template-dependent DNA synthesis across the broken ends, stabilizing the paired structure.
Polymerase theta's mutational signature
TMEJ is intrinsically
mutagenic
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer i ...
, since polymerase theta uses homologous
nucleotides
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...
from both break ends to initiate repair, which leads to loss of one set of these nucleotides in the DNA sequence. Therefore, TMEJ is a form of
micro-homology mediated end joining (MMEJ). Moreover, when break ends are not stabilized properly, the break ends can detach after polymerization. When these polymerized ends anneal again, a templated
insert Insert may refer to:
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*Insert key on a computer keyboard, used to switch between insert mode and overtype mode
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arises between the deletion junctions.
Reverse transcription of RNA
Polθ promotes RNA-templated
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
. Previously,
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 crea ...
s were long thought to only transcribe DNA into DNA or RNA and not be able to write
RNA segments into
DNA.
References
Further reading
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