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
Citations
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Re-evaluation of the linear no-threshold (LNT) model using new paradigms and modern molecular studies.
TL;DR: The evidence presented in this review reveals that there are minimal health risks with LDR exposure, and that a dose higher than some threshold value is necessary to achieve the harmful effects classically observed with high doses of radiation.
Journal ArticleDOI
The role of ATM and 53BP1 as predictive markers in cervical cancer.
Frank Roossink,Hylke W. Wieringa,Maartje G. Noordhuis,Klaske A. ten Hoor,Mirjam Kok,Lorian Slagter-Menkema,Harry Hollema,Geertruida H. de Bock,Elisabeth Pras,Elisabeth G.E. de Vries,Steven de Jong,Ate G.J. van der Zee,Ed Schuuring,G. Bea A. Wisman,Marcel A. T. M. van Vugt +14 more
TL;DR: Both in vitro and patient‐related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (Chemo) Radiation.
Journal ArticleDOI
Mesenchymal stem cells in acute myeloid leukemia: a focus on mechanisms involved and therapeutic concepts.
TL;DR: This review explains the anti-tumorigenic effects of MSCs through the suppression of tumor cell proliferation in hematological malignancies, especially in acute myeloid leukemia.
Journal ArticleDOI
Mathematical modeling and sensitivity analysis of G1/S phase in the cell cycle including the DNA-damage signal transduction pathway.
TL;DR: A novel mathematical model is constructed which integrated G1/S-checkpoint model with a signal transduction of DNA damage model and performed some numerical simulations which suggested that proposed model is biologically appropriate.
Journal ArticleDOI
Medicine: aborting the birth of cancer.
TL;DR: It is found that early stages of cancer development are associated with an active DNA damage response and p53-dependent cell death, and activation of the DNA damage checkpoint occurs before chromosome instability and malignancy.
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.