Next Article in Journal
Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders
Next Article in Special Issue
Regulation of BLM Nucleolar Localization
Previous Article in Journal
Molecular Inconsistencies in a Fragile X Male with Early Onset Ataxia
Previous Article in Special Issue
Reappearance from Obscurity: Mammalian Rad52 in Homologous Recombination
Article Menu

Export Article

Open AccessReview
Genes 2016, 7(9), 67;

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
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)
Full-Text   |   PDF [2431 KB, uploaded 21 September 2016]   |  


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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top