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DNA Polymerase θ: A Unique Multifunctional End-Joining Machine

Fels Institute for Cancer Research, Department of Medical Genetics and Molecular Biochemistry, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA
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Author to whom correspondence should be addressed.
Academic Editor: Paolo Cinelli
Received: 11 August 2016 / Revised: 2 September 2016 / Accepted: 8 September 2016 / Published: 21 September 2016
(This article belongs to the Special Issue Replication and Transcription Associated DNA Repair)
The gene encoding DNA polymerase θ (Polθ) was discovered over ten years ago as having a role in suppressing genome instability in mammalian cells. Studies have now clearly documented an essential function for this unique A-family polymerase in the double-strand break (DSB) repair pathway alternative end-joining (alt-EJ), also known as microhomology-mediated end-joining (MMEJ), in metazoans. Biochemical and cellular studies show that Polθ exhibits a unique ability to perform alt-EJ and during this process the polymerase generates insertion mutations due to its robust terminal transferase activity which involves template-dependent and independent modes of DNA synthesis. Intriguingly, the POLQ gene also encodes for a conserved superfamily 2 Hel308-type ATP-dependent helicase domain which likely assists in alt-EJ and was reported to suppress homologous recombination (HR) via its anti-recombinase activity. Here, we review our current knowledge of Polθ-mediated end-joining, the specific activities of the polymerase and helicase domains, and put into perspective how this multifunctional enzyme promotes alt-EJ repair of DSBs formed during S and G2 cell cycle phases. View Full-Text
Keywords: DNA polymerase; DNA repair; microhomology-mediated end-joining; alternative end-joining; replication repair; genome instability; cancer DNA polymerase; DNA repair; microhomology-mediated end-joining; alternative end-joining; replication repair; genome instability; cancer
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MDPI and ACS Style

Black, S.J.; Kashkina, E.; Kent, T.; Pomerantz, R.T. DNA Polymerase θ: A Unique Multifunctional End-Joining Machine. Genes 2016, 7, 67. https://0-doi-org.brum.beds.ac.uk/10.3390/genes7090067

AMA Style

Black SJ, Kashkina E, Kent T, Pomerantz RT. DNA Polymerase θ: A Unique Multifunctional End-Joining Machine. Genes. 2016; 7(9):67. https://0-doi-org.brum.beds.ac.uk/10.3390/genes7090067

Chicago/Turabian Style

Black, Samuel J., Ekaterina Kashkina, Tatiana Kent, and Richard T. Pomerantz 2016. "DNA Polymerase θ: A Unique Multifunctional End-Joining Machine" Genes 7, no. 9: 67. https://0-doi-org.brum.beds.ac.uk/10.3390/genes7090067

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