Translator Disclaimer
1 August 2009 Lack of DNA Polymerase θ (POLQ) Radiosensitizes Bone Marrow Stromal Cells In Vitro and Increases Reticulocyte Micronuclei after Total-Body Irradiation
Julie P. Goff, Donna S. Shields, Mineaki Seki, Serah Choi, Michael W. Epperly, Tracy Dixon, Hong Wang, Christopher J. Bakkenist, Stephen D. Dertinger, Dorothea K. Torous, John Wittschieben, Richard D. Wood, Joel S. Greenberger
Author Affiliations +
Abstract

Mammalian POLQ (pol θ) is a specialized DNA polymerase with an unknown function in vivo. Roles have been proposed in chromosome stability, as a backup enzyme in DNA base excision repair, and in somatic hypermutation of immunoglobulin genes. The purified enzyme can bypass AP sites and thymine glycol. Mice defective in POLQ are viable and have been reported to have elevated spontaneous and radiation-induced frequencies of micronuclei in circulating red blood cells. To examine the potential roles of POLQ in hematopoiesis and in responses to oxidative stress responses, including ionizing radiation, bone marrow cultures and marrow stromal cell lines were established from Polq / and Polq−/− mice. Aging of bone marrow cultures was not altered, but Polq−/− cells were more sensitive to γ radiation than were Polq / cells. The D0 was 1.38 ± 0.06 Gy for Polq / cells compared to 1.27 ± 0.16 and 0.98 ± 0.10 Gy (P  =  0.032) for two Polq−/− clones. Polq−/− cells were moderately more sensitive to bleomycin than Polq / cells and were not hypersensitive to paraquat or hydrogen peroxide. ATM kinase activation appeared to be normal in γ-irradiated Polq−/− cells. Inhibition of ATM kinase activity increased the radiosensitivity of Polq / cells slightly but did not affect Polq−/− cells. Polq−/− mice had more spontaneous and radiation-induced micronucleated reticulocytes than Polq / and /− mice. The sensitivity of POLQ-defective bone marrow stromal cells to ionizing radiation and bleomycin and the increase in micronuclei in red blood cells support a role for this DNA polymerase in cellular tolerance of DNA damage that can lead to double-strand DNA breaks.

Julie P. Goff, Donna S. Shields, Mineaki Seki, Serah Choi, Michael W. Epperly, Tracy Dixon, Hong Wang, Christopher J. Bakkenist, Stephen D. Dertinger, Dorothea K. Torous, John Wittschieben, Richard D. Wood, and Joel S. Greenberger "Lack of DNA Polymerase θ (POLQ) Radiosensitizes Bone Marrow Stromal Cells In Vitro and Increases Reticulocyte Micronuclei after Total-Body Irradiation," Radiation Research 172(2), 165-174, (1 August 2009). https://doi.org/10.1667/RR1598.1
Received: 17 September 2008; Accepted: 1 March 2009; Published: 1 August 2009
JOURNAL ARTICLE
10 PAGES


Share
SHARE
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top