Dual roles for DNA polymerase η in homologous DNA recombination and translesion DNA synthesis

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Abstract

Chicken B lymphocyte precursors and DT40 cells diversify their immunoglobulin-variable (IgV) genes through homologous recombination (HR)-mediated Ig gene conversion. To identify DNA polymerases that are involved in Ig gene conversion, we created DT40 clones deficient in DNA polymerase η (polη), which, in humans, is defective in the variant form of xeroderma pigmentosum (XP-V). Polη is an error-prone translesion DNA synthesis polymerase that can bypass UV damage-induced lesions and is involved in IgV hypermutation. Like XP-V cells, polη-disrupted (polη) clones exhibited hypersensitivity to UV. Remarkably, polη cells showed a significant decrease in the frequency of both Ig gene conversion and double-strand break-induced HR when compared to wild-type cells, and these defects were reversed by complementation with human polη. Our findings identify a DNA polymerase that carries out DNA synthesis for physiological HR and provides evidence that a single DNA polymerase can play multiple cellular roles. Copyright © 2005 by Elsevier Inc.

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Kawamoto, T., Araki, K., Sonoda, E., Yamashita, Y. M., Harada, K., Kikuchi, K., … Takeda, S. (2005). Dual roles for DNA polymerase η in homologous DNA recombination and translesion DNA synthesis. Molecular Cell, 20(5), 793–799. https://doi.org/10.1016/j.molcel.2005.10.016

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