ATR Regulates Fragile Site Stability
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TLDR
It is proposed that fragile sites are unreplicated chromosomal regions resulting from stalled forks that escape the ATR replication checkpoint, and have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells.About:
This article is published in Cell.The article was published on 2002-12-13 and is currently open access. It has received 565 citations till now. The article focuses on the topics: Chromosomal fragile site & Chromosome Fragile Site.read more
Citations
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Journal ArticleDOI
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
TL;DR: The molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed and apoptosis, which eliminates heavily damaged or seriously deregulated cells, is analyzed.
Journal ArticleDOI
DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
Jirina Bartkova,Zuzana Horejsi,Karen Koed,Alwin Krämer,Frederic Tort,Karsten Zieger,Per Guldberg,Maxwell Sehested,Jahn M. Nesland,Claudia Lukas,Torben F. Ørntoft,Jiri Lukas,Jiri Bartek +12 more
TL;DR: It is shown that in clinical specimens from different stages of human tumours of the urinary bladder, breast, lung and colon, the early precursor lesions commonly express markers of an activated DNA damage response.
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.
Journal ArticleDOI
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
Maria Eriksson,W. Ted Brown,Leslie B. Gordon,Leslie B. Gordon,Michael W. Glynn,Joel Singer,Laura J. Scott,Michael R. Erdos,Christiane M. Robbins,Tracy Moses,Peter Berglund,Amalia Dutra,Evgenia Pak,Sandra G. Durkin,Antonei B. Csoka,Michael Boehnke,Thomas W. Glover,Francis S. Collins +17 more
TL;DR: Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
Journal ArticleDOI
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Nikolaos G. Kastrinakis,Brynn Levy,Dimitris Kletsas,Akihiro Yoneta,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Thanos D. Halazonetis +15 more
TL;DR: A panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis as discussed by the authors.
References
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Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
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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.
Journal ArticleDOI
Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint
Qinghua Liu,Saritha Guntuku,Xian Shu Cui,Shuhei Matsuoka,David Cortez,Katsuyuki Tamai,Guangbin Luo,Sandra Carattini-Rivera,Francisco J. DeMayo,Allan Bradley,Lawrence A. Donehower,Stephen J. Elledge +11 more
TL;DR: It is shown that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU).
Journal ArticleDOI
Histone H2AX Is Phosphorylated in an ATR-dependent Manner in Response to Replicational Stress
Irene M. Ward,Junjie Chen +1 more
TL;DR: It is reported that inhibition of DNA replication by hydroxyurea or ultraviolet irradiation also induces phosphorylation and foci formation of H2AX, and these phospho-H2AX foci colocalize with proliferating cell nuclear antigen, BRCA1, and 53BP1 at the arrested replication fork in S phase cells.
Journal Article
Inhibition of ATM and ATR Kinase Activities by the Radiosensitizing Agent, Caffeine
Jann N. Sarkaria,Ericka C. Busby,Randal S. Tibbetts,Pia Roos,Yoichi Taya,Larry M. Karnitz,Robert T. Abraham +6 more
TL;DR: Caffeine inhibits the catalytic activity of both ATM and the related kinase, ATM and Rad3-related (ATR), at drug concentrations similar to those that induce radiosensitization, suggesting that both proteins are relevant targets for the development of novel anticancer agents.
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Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Nikolaos G. Kastrinakis,Brynn Levy,Dimitris Kletsas,Akihiro Yoneta,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Thanos D. Halazonetis +15 more