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  • Polymerase η suppresses telomere defects induced by DNA damaging agents.

Polymerase η suppresses telomere defects induced by DNA damaging agents.

Nucleic acids research (2014-10-31)
Hannah Pope-Varsalona, Fu-Jun Liu, Lynda Guzik, Patricia L Opresko
摘要

Telomeres at chromosome ends are normally masked from proteins that signal and repair DNA double strand breaks (DSBs). Bulky DNA lesions can cause DSBs if they block DNA replication, unless they are bypassed by translesion (TLS) DNA polymerases. Here, we investigated roles for TLS polymerase η, (polη) in preserving telomeres following acute physical UVC exposure and chronic chemical Cr(VI) exposure, which both induce blocking lesions. We report that polη protects against cytotoxicity and replication stress caused by Cr(VI), similar to results with ultraviolet C light (UVC). Both exposures induce ataxia telangiectasia and Rad3-related (ATR) kinase and polη accumulation into nuclear foci and localization to individual telomeres, consistent with replication fork stalling at DNA lesions. Polη-deficient cells exhibited greater numbers of telomeres that co-localized with DSB response proteins after exposures. Furthermore, the genotoxic exposures induced telomere aberrations associated with failures in telomere replication that were suppressed by polη. We propose that polη's ability to bypass bulky DNA lesions at telomeres is critical for proper telomere replication following genotoxic exposures.

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Sigma-Aldrich
Taq DNA聚合酶 来源于水生栖热菌, with 10× PCR reaction buffer containing MgCl2
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Taq DNA聚合酶 来源于水生栖热菌, with 10× PCR reaction buffer without MgCl2
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铬, chips, 99.995% trace metals basis
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铬, powder, ≥99% trace metals basis, <45 μm
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DNA 聚合酶 I, Klenow 片段 来源于大肠杆菌, buffered aqueous glycerol solution
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铬, powder, 99.5%, −100 mesh
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DNA Polymerase I from Escherichia coli lysogenic for NM 964, buffered aqueous glycerol solution
Sigma-Aldrich
铬, chips, thickness ~2 mm, 99.5%
铬, rod, 10mm, diameter 5.0mm, 99.7+%
铬, foil, light tested, 25x25mm, thickness 0.05mm, permanent polyester support, 99.99+%
铬, foil, light tested, 25x25mm, thickness 0.075mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.0125mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.015mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.01mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.025mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.02mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.03mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 100x100mm, thickness 0.04mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.0015mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.001mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.0025mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.002mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.003mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.004mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.005mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.007mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.009mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.0125mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.015mm, permanent polyester support, 99.99+%
铬, foil, not light tested, 25x25mm, thickness 0.01mm, permanent polyester support, 99.99+%