Functional human telomeres are recognized as DNA damage in G2 of the cell cycle.
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TL;DR: It is proposed that a localized DNA damage response at telomeres after replication is essential for recruiting the processing machinery that promotes formation of a chromosome end protection complex.
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About: This article is published in Molecular Cell. The article was published on 23 Nov 2005. and is currently open access. The article focuses on the topics: MRN complex & DNA damage.
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Citations
RAD52 and SLX4 act nonepistatically to ensure telomere stability during alternative telomere lengthening
Priyanka Verma,Robert L. Dilley,Tianpeng Zhang,Melina Theoni Gyparaki,Yiwen Li,Roger A. Greenberg +5 more
TL;DR: It is established that RAD52 and SLX4 mediate distinct postreplicative DNA repair processes that maintain ALT telomere stability and cancer cell viability.
Single molecule studies of physiologically relevant telomeric tails reveal POT1 mechanism for promoting G-quadruplex unfolding
Hong Wang,Gerald J. Nora,Gerald J. Nora,Harshad Ghodke,Harshad Ghodke,Patricia L. Opresko,Patricia L. Opresko +6 more
TL;DR: It is observed that the majority of the telomeric tails of 16 repeats formed two quadruplexes even though four were possible, indicating a novel POT1 activity beyond simply preventing quadruplex folding.
98
Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.
TL;DR: A detailed review of current knowledge on the MRN complex, kinases engaged in DNA repair, and genome instability disorders is presented.
95
A three-state model of telomere control over human proliferative boundaries
Anthony J. Cesare,Jan Karlseder +1 more
TL;DR: In this model telomeres facilitate a controlled permanent cell cycle arrest with a stable diploid genome during differentiation and may serve as an epigenetic sensor of general stress in DNA metabolism processes.
95
Chromatin Structure in Telomere Dynamics
TL;DR: Recent findings on chromatin modifications associated with the dynamic changes of telomeres from protected to deprotected state and their role in telomere functions are reviewed.
90
References
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.
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Cell-cycle checkpoints and cancer
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TL;DR: 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.
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Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith,Laurey Comeau,Soraya Rosenfield,Rachel M. Stansel,Alessandro Bianchi,Heidi Moss,Titia de Lange +6 more
TL;DR: Electron microscopy reported here demonstrated that TRF2 can remodel linear telomeric DNA into large duplex loops (t loops) in vitro, which may provide a general mechanism for the protection and replication of telomeres.
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Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Christine E. Canman,Dae-Sik Lim,Karlene A. Cimprich,Yoichi Taya,Katsuyuki Tamai,Kazuyasu Sakaguchi,Ettore Appella,Michael B. Kastan,Janet D. Siliciano +8 more
TL;DR: The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents, such as ionizing radiation, but not ultraviolet radiation as discussed by the authors.
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Cell cycle checkpoint signaling through the ATM and ATR kinases
TL;DR: These checkpoints contain, as their most proximal signaling elements, sensor proteins that scan chromatin for partially replicated DNA, DNA strand breaks, or other abnormalities, and translate these DNA-derived stimuli into biochemical signals that modulate the functions of specific downstream target proteins.