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DNA Polymerase θ: A Unique Multifunctional End-Joining Machine

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...

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Autores principales: Black, Samuel J., Kashkina, Ekaterina, Kent, Tatiana, Pomerantz, Richard T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042397/
https://www.ncbi.nlm.nih.gov/pubmed/27657134
http://dx.doi.org/10.3390/genes7090067
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author Black, Samuel J.
Kashkina, Ekaterina
Kent, Tatiana
Pomerantz, Richard T.
author_facet Black, Samuel J.
Kashkina, Ekaterina
Kent, Tatiana
Pomerantz, Richard T.
author_sort Black, Samuel J.
collection PubMed
description 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.
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spelling pubmed-50423972016-09-29 DNA Polymerase θ: A Unique Multifunctional End-Joining Machine Black, Samuel J. Kashkina, Ekaterina Kent, Tatiana Pomerantz, Richard T. Genes (Basel) Review 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. MDPI 2016-09-21 /pmc/articles/PMC5042397/ /pubmed/27657134 http://dx.doi.org/10.3390/genes7090067 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Black, Samuel J.
Kashkina, Ekaterina
Kent, Tatiana
Pomerantz, Richard T.
DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title_full DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title_fullStr DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title_full_unstemmed DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title_short DNA Polymerase θ: A Unique Multifunctional End-Joining Machine
title_sort dna polymerase θ: a unique multifunctional end-joining machine
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042397/
https://www.ncbi.nlm.nih.gov/pubmed/27657134
http://dx.doi.org/10.3390/genes7090067
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