Cells with dysfunctional telomeres are susceptible to reactive oxygen species hydrogen peroxide via generation of multichromosomal fusions and chromosomal fragments bearing telomeres

Woo, Seon Rang; Park, Jeong Eun; Juhn, Kyoung Mi; Ju, Yeun Jin; Jeong, Jae‐Weon; Kang, Chang Mo; Yun, Hyun Jin; Yun, Mi Yong; Shin, Hyun Jin; Joo, Hyun Jin; Park, Eun Ran; Park, In-Cheol; Hong, Sung Hee; Hwang, Sang‐Gu; Kim, Haekwon; Cho, Myung‐Haing; Kim, Sang Hoon; Park, Gil Hong; Lee, Kee Ho

doi:10.1016/j.bbrc.2011.11.086

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…Regarding radiotherapy, it should be noted that drugs that could specifically sensitise tumours to ionising radiations, and in particular radioresistant tumours such as glioblastomas (GBM), would greatly enhance our ability to deliver curative doses while avoiding off-target effects. In general, an increased sensitivity to reactive oxygen species [32], the radiomimetic agent bleomycin [33] and ionising radiations [6,7,34] has been shown in cells with dysfunctional telomeres and/or short telomeres. Therefore, telomere dysfunction has been proposed as new a factor in the sensitivity to ionising radiation treatment [35,36].…”

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confidence: 99%

The G-quadruplex-stabilising agent RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells

et al. 2015

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mentioning

confidence: 99%

The G-quadruplex-stabilising agent RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells

et al. 2015

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“…Mammalian cells with shortened telomeres exhibit increased sensitivity to DNA-damaging agents via an as-yet-unknown mechanism (Goytisolo et al 2000;Wong et al 2000;GonzalezSuarez et al 2003;Nakamura et al 2005;Agarwal et al 2008;Soler et al 2009;Drissi et al 2011;Woo et al 2012). Based on this precedent, we hypothesized that resistance to DNA-damaging agents in yeast would also be tightly linked to telomere length and that yeast cells would become more sensitive to DNA damage in a progressive manner as telomeres shorten.…”

Section: Loss Of Telomerase Is Associated With a Progressive Increasementioning

confidence: 99%

Novel Connections Between DNA Replication, Telomere Homeostasis, and the DNA Damage Response Revealed by a Genome-Wide Screen for TEL1/ATM Interactions in Saccharomyces cerevisiae

2013

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Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-D cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood. To address the first question, we present the results from a comprehensive genome-wide screen for genetic interactions with tel1-D that cause sensitivity to methyl methanesulfonate (MMS) and/or ionizing radiation, along with follow-up characterizations of the 13 interactions yielded by this screen. Surprisingly, many of the tel1-D interactions that confer DNA damage sensitivity also exacerbate the short telomere phenotype, suggesting a connection between these two phenomena. Restoration of normal telomere length in the tel1-D xxx-D mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length.In support of a model for increased replication stress in the tel1-D xxx-D mutants, we show that depletion of dNTP pools through pretreatment with hydroxyurea renders tel1-D cells (but not wild type) MMS-sensitive, demonstrating that, under certain conditions, Tel1p does indeed play a critical role in the DDR.

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SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

Joo

Woo

Shen

et al. 2012

Biochemical and Biophysical Research Communications

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Cells with dysfunctional telomeres are susceptible to reactive oxygen species hydrogen peroxide via generation of multichromosomal fusions and chromosomal fragments bearing telomeres

Cited by 3 publications

References 27 publications

The G-quadruplex-stabilising agent RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells

The G-quadruplex-stabilising agent RHPS4 induces telomeric dysfunction and enhances radiosensitivity in glioblastoma cells

Novel Connections Between DNA Replication, Telomere Homeostasis, and the DNA Damage Response Revealed by a Genome-Wide Screen for TEL1/ATM Interactions in Saccharomyces cerevisiae

SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

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