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Reference: Nicolay, NH, Carter, R, Hatch, SB et al., (2012). Homologous recombination mediates S-phase-dependent radioresistance in cells deficient in DNA polymerase eta. Carcinogenesis, 33 (11), 2026-2034.Citable link to this page:

 

Homologous recombination mediates S-phase-dependent radioresistance in cells deficient in DNA polymerase eta.

Abstract: DNA polymerase eta (pol η) is the only DNA polymerase causally linked to carcinogenesis in humans. Inherited deficiency of pol η in the variant form of xeroderma pigmentosum (XPV) predisposes to UV-light-induced skin cancer. Pol η-deficient cells demonstrate increased sensitivity to cisplatin and oxaliplatin chemotherapy. We have found that XP30R0 fibroblasts derived from a patient with XPV are more resistant to cell kill by ionising radiation (IR) than the same cells complemented with wild-type pol η. This phenomenon has been confirmed in Burkitt's lymphoma cells, which either expressed wild-type pol η or harboured a pol η deletion. Pol η deficiency was associated with accumulation of cells in S-phase, which persisted after IR. Cells deficient in pol η demonstrated increased homologous recombination (HR)-directed repair of double strand breaks created by IR. Depletion of the HR protein, X-ray repair cross-complementing protein 3 (XRCC3), abrogated the radioresistance observed in pol η-deficient cells as compared with pol η-complemented cells. These findings suggest that HR mediates S-phase-dependent radioresistance associated with pol η deficiency. We propose that pol η protein levels in tumours may potentially be used to identify patients who require treatment with chemo-radiotherapy rather than radiotherapy alone for adequate tumour control.

Publication status:Published

Bibliographic Details

Journal: Carcinogenesissee more from them

Issue Date: 2012-11

pages:2026-2034Identifiers

Urn: uuid:636c696c-33b8-4402-a165-a46f3b3c957e

Source identifier: 350545

Eissn: 1460-2180

Doi: https://doi.org/10.1093/carcin/bgs239

Issn: 0143-3334 Item Description

Type: Journal article;

Language: eng Keywords: Humans Fibroblasts Cells, Cultured RNA, Small Interfering DNA-Directed DNA Polymerase DNA-Binding Proteins Nucleic Acid Synthesis Inhibitors Flow Cytometry Tumor Stem Cell Assay Blotting, Western Apoptosis Cell Proliferation S Phase Neoplasms Gamma Rays Radiation Tolerance DNA Damage DNA Repair Homologous Recombination Tiny URL: pubs:350545

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Autor: Nicolay, NH - - - Carter, R - - - Hatch, SB - - - Schultz, N - - - Prevo, R - - - Mckenna, WG - institutionUniversity of Oxford O

Fuente: https://ora.ox.ac.uk/objects/uuid:636c696c-33b8-4402-a165-a46f3b3c957e



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