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POLQ

Protein-coding gene in the species Homo sapiens


Summary

Protein-coding gene in the species Homo sapiens

DNA polymerase theta is an enzyme that in humans is encoded by the POLQ gene. 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 (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, since polymerase theta uses homologous nucleotides 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 arises between the deletion junctions.

Reverse transcription of RNA

Polθ promotes RNA-templated DNA repair. Previously, DNA polymerases were long thought to only transcribe DNA into DNA or RNA and not be able to write RNA segments into DNA.

References

References

  1. (July 1999). "Cloning and chromosomal mapping of the human DNA polymerase theta (POLQ), the eighth human DNA polymerase". Genomics.
  2. "Entrez Gene: POLQ polymerase (DNA directed), theta".
  3. (July 2010). "Dual roles for DNA polymerase theta in alternative end-joining repair of double-strand breaks in Drosophila". PLOS Genetics.
  4. (September 2010). "Synthesis-dependent microhomology-mediated end joining accounts for multiple types of repair junctions". Nucleic Acids Research.
  5. (2014-02-05). "A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites". Nature Communications.
  6. (June 2014). "Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans". Genome Research.
  7. (September 2019). "Templated Insertions: A Smoking Gun for Polymerase Theta-Mediated End Joining". Trends in Genetics.
  8. (October 2014). "Mechanism of suppression of chromosomal instability by DNA polymerase POLQ". PLOS Genetics.
  9. (February 2015). "Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination". Nature.
  10. (February 2015). "Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair". Nature.
  11. (September 2019). "Templated Insertions: A Smoking Gun for Polymerase Theta-Mediated End Joining". Trends in Genetics.
  12. "New discovery shows human cells can write RNA sequences into DNA". phys.org.
  13. (June 2021). "Polθ reverse transcribes RNA and promotes RNA-templated DNA repair". Science Advances.
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This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

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