Journal ArticleDOI
Cell-cycle checkpoints and cancer
Michael B. Kastan,Jiri Bartek +1 more
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TLDR
All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation, and how cells respond to DNA damage are critical determinants of whether that individual will develop cancer.Abstract:
All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation. Highly conserved DNA-repair and cell-cycle checkpoint pathways allow cells to deal with both endogenous and exogenous sources of DNA damage. How much an individual is exposed to these agents and how their cells respond to DNA damage are critical determinants of whether that individual will develop cancer. These cellular responses are also important for determining toxicities and responses to current cancer therapies, most of which target the DNA.read more
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Recurrent chemical reactivations of EBV promotes genome instability and enhances tumor progression of nasopharyngeal carcinoma cells
Chih Yeu Fang,Chia Huei Lee,Chung-Chun Wu,Yu-Ting Chang,Shu Ling Yu,Sheng Ping Chou,Ping Ting Huang,Chi Long Chen,Jia Woei Hou,Yao Chang,Ching-Hwa Tsai,Kenzo Takada,Jen Yang Chen,Jen Yang Chen +13 more
TL;DR: Recurrent reactivations of EBV in NA and HA cells resulted in a marked increase of genome instability and a profound increase in both characteristics of the repeatedly reactivated NA cells, suggesting that recurrent EBV reactivation may result in accumulation of genome stability and promote the tumor progression of NPC.
Journal ArticleDOI
Telomere dysfunction drives aberrant hematopoietic differentiation and myelodysplastic syndrome
Simona Colla,Derrick Sek Tong Ong,Yamini Ogoti,Matteo Marchesini,Nipun A. Mistry,Karen Clise-Dwyer,Sonny Ang,Paola Storti,Paola Storti,Andrea Viale,Nicola Giuliani,Kathryn Ruisaard,Irene Ganan Gomez,Christopher A. Bristow,Marcos R. Estecio,David C. Weksberg,Yan Wing Ho,Baoli Hu,Giannicola Genovese,Piergiorgio Pettazzoni,Asha S. Multani,Shan Jiang,Sujun Hua,Michael Ryan,Alessandro Carugo,Luigi Nezi,Yue Wei,Hui Yang,Marianna D'Anca,Li Zhang,Sarah Gaddis,Ting Gong,James W. Horner,Timothy P. Heffernan,Philip Jones,Laurence J.N. Cooper,Han Liang,Hagop M. Kantarjian,Y. Alan Wang,Lynda Chin,Carlos Bueso-Ramos,Guillermo Garcia-Manero,Ronald A. DePinho +42 more
TL;DR: The genetic evidence that telomere dysfunction-induced DNA damage drives classical MDS phenotypes and alters common myeloid progenitor (CMP) differentiation by repressing the expression of mRNA splicing/processing genes, including SRSF2 is provided.
Journal ArticleDOI
High red meat diets induce greater numbers of colonic DNA double-strand breaks than white meat in rats: attenuation by high-amylose maize starch.
TL;DR: Dietary red meat causes greater levels of colonic DNA SSB and DSB than white meat, consistent with the epidemiological data, and resistant starch, a dietary fibre component, provides protection against this damage.
Journal Article
Enhancement of radiation response in p53 deficient cancer cells by the Aurora-B kinase inhibitor AZD1152
TL;DR: Data indicate that AZD1152 can radiosensitize tumor cell lines in vitro and in vivo, and the fact that these effects are exacerbated in p53-deficient cancer cells is of potential interest for further clinical development.
Journal ArticleDOI
Activation of the ATM-Snail pathway promotes breast cancer metastasis
Mianen Sun,Xiaojing Guo,Xiaojing Guo,Xiaolong Qian,Haibo Wang,Chunying Yang,Kathryn L. Brinkman,Monica Serrano-Gonzalez,Richard S. Jope,Binhua Zhou,David A. Engler,Ming Zhan,Stephen T. C. Wong,Li Fu,Bo Xu +14 more
TL;DR: It is demonstrated that the ATM kinase, one of the critical DDR elements, is hyperactive in late stage breast tumor tissues with lymph-node metastasis and this hyperactivity correlates with elevated expression of the epithelial-mesenchymal transition marker, Snail.
References
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Book
The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today
Richard Doll,Richard Peto +1 more
TL;DR: Evidence that the various common types of cancer are largely avoidable diseases is reviewed, and it is suggested that, apart from cancer of the respiratory tract, the types of cancers that are currently common are not peculiarly modern diseases and are likely to depend chiefly on some long-established factor.
Journal ArticleDOI
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
TL;DR: It is shown that ATM is held inactive in unirradiated cells as a dimer or higher-order multimer, with the kinase domain bound to a region surrounding serine 1981 that is contained within the previously described ‘FAT’ domain.
Journal ArticleDOI
Checkpoints: controls that ensure the order of cell cycle events
Leland H. Hartwell,Ted Weinert +1 more
TL;DR: It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose special problems for the fidelity of embryonic cell division.
Journal ArticleDOI
Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes
Lee Zou,Stephen J. Elledge +1 more
TL;DR: The data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling.
Journal ArticleDOI
ATM and related protein kinases: safeguarding genome integrity
TL;DR: Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.