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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Journal ArticleDOI
Molecular theory of cancer.
TL;DR: This review discusses how somatically-heritable molecular alterations alter translation of cellular signals, resulting in resistance to growth inhibition and apoptosis, that is manifested as secondary hallmarks of cancer and as the amazing ability of some cancer cells such as canine transmissible sarcoma to ‘live in a wild’ like unicellular mammalian species.
Journal ArticleDOI
Bocavirus Infection Induces a DNA Damage Response That Facilitates Viral DNA Replication and Mediates Cell Death
TL;DR: It is reported that MVC infection triggers a DNA damage response in infected cells, as evident from phosphorylation of H2AX and RPA32, and the notion that an autonomous parvovirus is able to hijack the host DNA damage machinery for its own replication and for the induction of cell death is supported.
Journal ArticleDOI
Assessment of protein dynamics and DNA repair following generation of DNA double-strand breaks at defined genomic sites
TL;DR: A system using enzymatic creation of site-specific DNA DSBs within the human genome combined with chromatin immunoprecipitation (ChIP) that enables molecular probing of a DSB and direct measurement of DNA repair defects in human cells is described.
Journal ArticleDOI
ATM- and ATR-mediated phosphorylation of XRCC3 regulates DNA double-strand break-induced checkpoint activation and repair.
TL;DR: It is shown that an SQ motif serine 225 in XRCC3 is phosphorylated by ATR kinase in an ATM signaling pathway, and this modification follows end resection and is specific to S and G2 phases.
Journal ArticleDOI
The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints.
Marcia A. Munoz,Darren N. Saunders,Michelle J. Henderson,Jennifer L. Clancy,Amanda J. Russell,Gillian M. Lehrbach,Elizabeth A. Musgrove,Colin Watts,Robert L. Sutherland +8 more
TL;DR: It is demonstrated that EDD is necessary for G1/S and intra S phase DNA damage checkpoint activation and for the maintenance of G2/M arrest after double strand DNA breaks and the expression of several key cell cycle mediators was altered, suggesting that these checkpoint defects may be both CHK2-dependent and -independent.
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.