Initiating Cellular Stress Responses

Bakkenist, Christopher J.; Kastan, Michael B.

doi:10.1016/j.cell.2004.06.023

Cited by 436 publications

(384 citation statements)

References 50 publications

Supporting

Mentioning

373

Contrasting

Unclassified

Order By: Relevance

“…The DNA damage response network involves parallel modulation of a wide array of signaling pathways, including lesion processing and repair, activation of cell cycle checkpoints, the apoptotic pathway, and many less characterized stress signals (Shiloh, 2003;Bakkenist and Kastan, 2004). Characterization of gene expression profiles following DNA damage indicated a wider scope of transcriptional response to such damage than previously estimated (Jelinsky and Samson, 1999;Jelinsky et al, 2000;Gasch et al, 2001).…”

Section: Introductionmentioning

confidence: 94%

Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue

Rashi-Elkeles

Elkon

Weizman³

et al. 2005

Oncogene

View full text Add to dashboard Cite

The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia, is a master regulator of the cellular network induced by DNA double-strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combined gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation in murine lymphoid tissue. Cluster analysis revealed a prominent pattern characterizing dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of NF-jB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro-and antiapoptotic signals were simultaneously induced, with the proapoptotic pathway mediated by p53 targets, and the prosurvival pathway by NF-jB targets. These findings further elucidate the molecular network induced by IR, point to novel putative NF-jB targets, and suggest a mechanistic model for cellular balancing between pro-and antiapoptotic signals induced by IR in lymphoid tissues, which has implications for cancer management. The emerging model suggests that restoring the p53-mediated apoptotic arm while blocking the NF-jB-mediated prosurvival arm could effectively increase the radiosensitivity of lymphoid tumors.

show abstract

Section: Introductionmentioning

confidence: 94%

Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue

Rashi-Elkeles

Elkon

Weizman³

et al. 2005

Oncogene

View full text Add to dashboard Cite

show abstract

“…The gene defective in A-T is ataxia-telangiectasia mutated (ATM), a kinase that modulates the activity of a variety of substrates important for engaging the DNA damage response after DNA DSBs. ATM substrates have important functions for regulating cell cycle arrest and apoptosis (Shiloh, 2003(Shiloh, , 2006Bakkenist and Kastan, 2004). Tissue specificity is an important aspect of ATM function, and relates to the wide phenotypic spectrum present in A-T. For instance, some ATMdeficient tissues are extremely radiosensitive such as the intestine or hematopoietic system, while in contrast many ATM-deficient immature neurons are radioresistant (Frappart and McKinnon, 2006).…”

Section: Atm and The Dna Dsb Response During Developmentmentioning

confidence: 99%

DNA double-strand break repair and development

Phillips

McKinnon

2007

Oncogene

View full text Add to dashboard Cite

Normal development of an organism requires the ability to respond to DNA damage. A particularly deleterious lesion is a DNA double-strand break (DSB). The cellular response to DNA DSBs occurs via an integrated sensing and signaling network that maintains genomic stability. The outcomes of defective DNA DSB repair are related to the developmental stage of an organism, and often show striking tissue specificity. Many human diseases are associated with deficiencies in DNA DSB repair and can be characterized by neuropathology, immune deficiency, growth retardation or predisposition to cancer. This review will focus on the requirements of the DNA DSB response that function to maintain homeostasis during mammalian development.

show abstract

“…It nevertheless appears that the phenomenon of 'genetic memory' capable of destabilizing the nonexposed progeny of irradiated cells/organisms may result from a plethora of molecular, biochemical and cellular events, each of which could potentially represent the still unknown pathway(s) of cellular stress response. To date, a majority of pathways involved in the mammalian cellular response to radiation, including the recognition of DNA damage, its repair, cell cycle arrest and apoptosis, have been characterized (Friedberg et al, 1995;Bakkenist and Kastan, 2004;Sancar et al, 2004). However, the results of some publications show that the ability of cells to exhibit elevated mutation rates cannot be ascribed to the conventional mechanisms and is most likely related to the epigenetic events (Dubrova et al, 2000;Dubrova, 2003;Lorimore et al, 2003;Morgan, 2003a, b).…”

Section: Introductionmentioning

confidence: 99%

Radiation-induced transgenerational alterations in genome stability and DNA damage

et al. 2006

View full text Add to dashboard Cite

Mutation induction in directly exposed cells is currently regarded as the main component of the genetic risk of ionizing radiation for humans. However, recent data on the transgenerational increases in mutation rates in the offspring of irradiated parents indicate that the genetic risk could be greater than predicted previously. Here, we have analysed transgenerational changes in mutation rates and DNA damage in the germline and somatic tissues of non-exposed first-generation offspring of irradiated inbred male CBA/Ca and BALB/c mice. Mutation rates at an expanded simple tandem repeat DNA locus and a proteincoding gene (hprt) were significantly elevated in both the germline (sperm) and somatic tissues of all the offspring of irradiated males. The transgenerational changes in mutation rates were attributed to the presence of a persistent subset of endogenous DNA lesions (double-and singlestrand breaks), measured by the phosphorylated form of histone H2AX (c-H2AX) and alkaline Comet assays. Such remarkable transgenerational destabilization of the F 1 genome may have important implications for cancer aetiology and genetic risk estimates. Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability.

show abstract

Initiating Cellular Stress Responses

Cited by 436 publications

References 50 publications

Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue

Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue

DNA double-strand break repair and development

Radiation-induced transgenerational alterations in genome stability and DNA damage

Contact Info

Product

Resources

About