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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HP1 proteins are essential for a dynamic nuclear response that rescues the function of perturbed heterochromatin in primary human cells.
Rugang Zhang,Song-Tao Liu,Wei Chen,Michael F. Bonner,John R. Pehrson,Tim J. Yen,Peter D. Adams +6 more
TL;DR: It is shown that primary human cells respond to a variety of small molecules that perturb DNA and histone modifications by recruiting HP1 proteins to sites of altered pericentromeric heterochromatin, which is essential to maintain the HP1-binding kinetochore protein hMis12 at Kinetochores and to suppress catastrophic mitotic defects.
Journal ArticleDOI
HERC2-USP20 axis regulates DNA damage checkpoint through Claspin
Jian Yuan,Kuntian Luo,Min Deng,Yunhui Li,Ping Yin,Bowen Gao,Yuan Fang,Puqiang Wu,Tongzheng Liu,Tongzheng Liu,Zhenkun Lou +10 more
TL;DR: Findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling and deubiquitinates and stabilizes Claspin and enhances the activation of AtR-Chk1 signaling.
Journal ArticleDOI
Defective Cell Cycle Checkpoint Functions in Melanoma Are Associated with Altered Patterns of Gene Expression
William K. Kaufmann,Kathleen R. Nevis,Pingping Qu,Joseph G. Ibrahim,Tong Zhou,Yingchun Zhou,Dennis A. Simpson,Jennifer Helms-Deaton,Marila Cordeiro-Stone,Dominic T. Moore,Nancy E. Thomas,Honglin Hao,Zhi Liu,Janiel M. Shields,Glynis Scott,Norman E. Sharpless +15 more
TL;DR: The results suggest that defects in DNA damage checkpoints may be recognized in melanomas through analysis of gene expression, and a Bayesian analysis tool was more accurate than significance analysis of microarrays for predicting checkpoint function using a leave-one-out method.
Journal ArticleDOI
Dynamic Reorganization of the Cytoskeleton during Apoptosis: The Two Coffins Hypothesis.
Suleva Povea-Cabello,Manuel Oropesa-Ávila,Patricia de la Cruz-Ojeda,Marina Villanueva-Paz,Mario de la Mata,Juan M. Suárez-Rivero,Mónica Álvarez-Córdoba,Irene Villalón-García,David Cotán,Patricia Ybot-Gonzalez,José Antonio Sánchez-Alcázar +10 more
TL;DR: Round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses, suggesting that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response.
Journal ArticleDOI
Hsp70-2 is required for tumor cell growth and survival.
TL;DR: Data based on RNA interference technology has revealed that also Hsp70-2, a protein essential for spermatogenesis, is required for cancer cell growth and survival.
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.