DNA polymerase theta, also called POLQ, is a unique A-family polymerase that encodes a 290-kDa protein with an N-terminal helicase-like domain and a C-terminal DNA polymerase domain [1]. Its primary involvement lies in the repair mechanism of DNA double-strand breaks induced by fork collapse [1]. Notably, POLQ is involved in the repair of double-strand breaks provoked by external stressors [2]. Additionally, POLQ has been found to participate in the development and progression of human cancers due to its critical functions in repairing genomic double-strand breaks [3].
The overexpression of POLQ has emerged as a prognostic indicator in early-stage breast cancer patients, while also being identified as an oncoprotein in lung cancer cells [4][5]. Additionally, POLQ exhibits capabilities in enhancing resistance to DNA-protein crosslinking agents and possesses inherent 5'-deoxyribose phosphate (5'-dRP) lyase activity, which potentially operates in base excision repair processes [6][7].
Further investigations have unveiled POLQ's involvement in T-DNA integration within plant somatic cells, sparking interest in its function within hematopoietic cells and its correlation with radiation sensitivity [8][9]. Notably, POLQ may collaborate with other DNA polymerases, such as POLβ, in repairing oxidative DNA damage via base excision repair pathways [10]. However, despite these insights, the precise physiological functions governed by POLQ remain incompletely understood, necessitating continued research endeavors to unravel its multifaceted roles across various cellular processes [2].
References:
[1] Z. Wang, Y. Song, S. Li, S. Kurian, R. Xiang, T. Chibaet al., "Dna polymerase θ (polq) is important for repair of dna double-strand breaks caused by fork collapse", Journal of Biological Chemistry, vol. 294, no. 11, p. 3909-3919, 2019. https://doi.org/10.1074/jbc.ra118.005188
[2] S. Zhou, K. Wang, J. Wang, J. He, W. Zheng, C. Longet al., "Identification of novel biomarkers with diagnostic value and immune infiltration in burn injury", Frontiers in Genetics, vol. 13, 2022. https://doi.org/10.3389/fgene.2022.829841
[3] Q. Pan, L. Wang, Y. Liu, M. Li, Y. Zhang, P. Weiet al., "Knockdown of polq interferes the development and progression of hepatocellular carcinoma through regulating cell proliferation, apoptosis and migration",, 2020. https://doi.org/10.21203/rs.3.rs-58139/v1
[4] G. Higgins, A. Harris, R. Prevo, T. Helleday, W. McKenna, & F. Buffa, "Overexpression of polq confers a poor prognosis in early breast cancer patients", Oncotarget, vol. 1, no. 3, p. 175-184, 2010. https://doi.org/10.18632/oncotarget.124
[5] X. Rao, B. Xing, Z. Wu, Y. Bin, Y. Chen, Y. Xuet al., "Targeting polymerase θ impairs tumorigenesis and enhances radiosensitivity in lung adenocarcinoma", Cancer Science, vol. 114, no. 5, p. 1943-1957, 2023. https://doi.org/10.1111/cas.15727
[6] G. Chandramouly, S. Liao, T. Rusanov, N. Borisonnik, M. Calbert, T. Kentet al., "Polθ promotes the repair of 5′-dna-protein crosslinks by microhomology-mediated end-joining", Cell Reports, vol. 34, no. 10, p. 108820, 2021. https://doi.org/10.1016/j.celrep.2021.108820
[7] M. Hogg, M. Seki, R. Wood, S. Doublié, & S. Wallace, "Lesion bypass activity of dna polymerase θ (polq) is an intrinsic property of the pol domain and depends on unique sequence inserts", Journal of Molecular Biology, vol. 405, no. 3, p. 642-652, 2011. https://doi.org/10.1016/j.jmb.2010.10.041
[8] A. Nishizawa‐Yokoi, "Transformation and regeneration of dna polymerase θ mutant rice plants", Plant Direct, vol. 7, no. 9, 2023. https://doi.org/10.1002/pld3.526
[9] J. Goff, D. Shields, M. Seki, S. Choi, M. Epperly, T. Dixonet al., "Lack of dna polymerase θ (polq) radiosensitizes bone marrow stromal cellsin vitroand increases reticulocyte micronuclei after total-body irradiation", Radiation Research, vol. 172, no. 2, p. 165-174, 2009. https://doi.org/10.1667/rr1598.1
[10] M. Yoshimura, M. Kohzaki, J. Nakamura, K. Asagoshi, E. Sonoda, E. Houet al., "Vertebrate polq and polβ cooperate in base excision repair of oxidative dna damage", Molecular Cell, vol. 24, no. 1, p. 115-125, 2006. https://doi.org/10.1016/j.molcel.2006.07.032
