Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks

Lundin, C.; North, M.; Erixon, K.; Walters, K.; Jenssen, D.; Goldman, Alastair S. H.; Helleday, T.

doi:10.1093/nar/gks589

Cited by 80 publications

(92 citation statements)

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“…The high-energy γ-irradiation breaks the DNA strands directly and mainly involves the NHEJ repair pathway [15,16]. It is not fully confirmed whether MMS directly induces DSBs, but it stalls DNA replication and HR is involved in the repair of stalled replication forks [17]. DOX induces DNA damage through increased oxidative stress and by intercalating the DNA strands [18].…”

Section: Discussionmentioning

confidence: 99%

Extracellular ATP protects endothelial cells against DNA damage

Aho

Helenius

Vattulainen-Collanus

et al. 2016

Purinergic Signalling

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Cell damage can lead to rapid release of ATP to extracellular space resulting in dramatic change in local ATP concentration. Evolutionary, this has been considered as a danger signal leading to adaptive responses in adjacent cells.Our aim was to demonstrate that elevated extracellular ATP or inhibition of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be used to increase tolerance against DNA-damaging conditions. Human endothelial cells, with increased extracellular ATP concentration in cell proximity, were more resistant to irradiation or chemically induced DNA damage evaluated with the DNA damage markers γH2AX and phosphorylated p53. In our rat models of DNA damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage. Interestingly, the phenomenon could not be replicated in cancer cells. Our results show that transient increase in extracellular ATP can promote resistance to DNA damage.

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Section: Discussionmentioning

confidence: 99%

Extracellular ATP protects endothelial cells against DNA damage

Aho

Helenius

Vattulainen-Collanus

et al. 2016

Purinergic Signalling

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“…To rule out the possibility that VirE2-expressing lines are more prone to general stress that might have contributed to increased sensitivity to bleomycin, the plants were exposed to MMS. MMS is an alkylating agent that causes heat-labile DNA damage but not DSBs (Lundin et al, 2005). As shown in Supplemental Figure 7 online, there was no significant difference in the response of Col-0 and VirE2-expressing lines to MMS at the two different concentrations tested.…”

Section: Arabidopsis Plants Expressing Vire2 Are Hypersensitive To Blmentioning

confidence: 90%

Agrobacterium May Delay Plant Nonhomologous End-Joining DNA Repair via XRCC4 to Favor T-DNA Integration

et al. 2012

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Agrobacterium tumefaciens is a soilborne pathogen that causes crown gall disease in many dicotyledonous plants by transfer of a portion of its tumor-inducing plasmid (T-DNA) into the plant genome. Several plant factors that play a role in Agrobacterium attachment to plant cells and transport of T-DNA to the nucleus have been identified, but the T-DNA integration step during transformation is poorly understood and has been proposed to occur via nonhomologous end-joining (NHEJ)-mediated doublestrand DNA break (DSB) repair. Here, we report a negative role of X-RAY CROSS COMPLEMENTATION GROUP4 (XRCC4), one of the key proteins required for NHEJ, in Agrobacterium T-DNA integration. Downregulation of XRCC4 in Arabidopsis and Nicotiana benthamiana increased stable transformation due to increased T-DNA integration. Overexpression of XRCC4 in Arabidopsis decreased stable transformation due to decreased T-DNA integration. Interestingly, XRCC4 directly interacted with Agrobacterium protein VirE2 in a yeast two-hybrid system and in planta. VirE2-expressing Arabidopsis plants were more susceptible to the DNA damaging chemical bleomycin and showed increased stable transformation. We hypothesize that VirE2 titrates or excludes active XRCC4 protein available for DSB repair, thus delaying the closure of DSBs in the chromosome, providing greater opportunity for T-DNA to integrate.

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“…Embryonic fibroblasts were cultured with methyl methanesulfonate (MMS) (Sigma, Japan) for 24 h (11), then the viable cell number was determined on trypan blue.…”

Section: Blm-deficient Embryonic Fibroblastsmentioning

confidence: 99%

Augmented cell death with Bloom syndrome helicase deficiency

et al. 2011

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Abstract. Bloom syndrome (BS) is a rare autosomal genetic disorder characterized by lupus-like erythematous telangiectasias of the face, sun sensitivity, infertility, stunted growth, upper respiratory infection, and gastrointestinal infections commonly associated with decreased immuno globulin levels. The syndrome is associated with immuno deficiency of a generalized type, ranging from mild and essentially asymptomatic to severe. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BS is caused by mutations in BLM, a member of the RecQ helicase family. �e deter�e determined whether BLM deficiency has any effects on cell growth and death in BLM-deficient cells and mice. BLM-deficient EB-virus-transformed cell lines from BS patients and embryonic fibroblasts from BLM -/-mice showed slower growth than wild-type cells. BLM-deficient cells showed abnormal p53 protein expression after irradiation. In BLM -/-mice, small body size, reduced number of fetal liver cells and increased cell death were observed. BLM deficiency causes the up-regulation of p53, double-strand break and apoptosis, which are likely observed in irradiated control cells. Slow cell growth and increased cell death may be one of the causes of the small body size associated with BS patients.

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Methyl methanesulfonate (MMS) produces heat-labile DNA damage but no detectable in vivo DNA double-strand breaks

Cited by 80 publications

References 0 publications

Extracellular ATP protects endothelial cells against DNA damage

Extracellular ATP protects endothelial cells against DNA damage

Agrobacterium May Delay Plant Nonhomologous End-Joining DNA Repair via XRCC4 to Favor T-DNA Integration

Augmented cell death with Bloom syndrome helicase deficiency

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