Journal ArticleDOI
The Mre11 complex: at the crossroads of dna repair and checkpoint signalling.
TLDR
The Mre 11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2 and its functions in checkpoint signalling and DNA replication are uncovered.Abstract:
The Mre11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2. Mutations in the genes that encode components of this complex result in DNA- damage sensitivity, genomic instability, telomere shortening and aberrant meiosis. The molecular defect that underlies these phenotypes has long been thought to be related to a DNA repair deficiency. However, recent studies have uncovered functions for the Mre11 complex in checkpoint signalling and DNA replication.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
Cell-cycle checkpoints and cancer
Michael B. Kastan,Jiri Bartek +1 more
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.
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
Human CtIP promotes DNA end resection
Alessandro A. Sartori,Claudia Lukas,Julia Coates,Martin Mistrik,Shuang Fu,Jiri Bartek,Richard Baer,Jiri Lukas,Stephen P. Jackson +8 more
TL;DR: These findings establish evolutionarily conserved roles for CtIP-like proteins in controlling DSB resection, checkpoint signalling and homologous recombination.
Journal ArticleDOI
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage.
TL;DR: Findings reveal that recruitment of these PIKKs to DNA lesions occurs by common mechanisms through an evolutionarily conserved motif, and provide direct evidence that PIKK recruitment is required for PIKK-dependent DNA-damage signalling.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae
Frédéric Pâques,James E. Haber +1 more
TL;DR: This review encompasses different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.
Journal ArticleDOI
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.
Tanya T. Paull,Emmy P. Rogakou,Vikky Yamazaki,Cordula U. Kirchgessner,Martin Gellert,William M. Bonner +5 more
TL;DR: The evidence presented strongly supports a role for the gamma-H2AX and the PI-3 protein kinase family in focus formation at sites of double-strand breaks and suggests the possibility of a change in chromatin structure accompanying double-Strand break repair.
Journal ArticleDOI
The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.
James P. Carney,James P. Carney,Richard S. Maser,Heidi A. Olivares,Elizabeth M. Davis,Michelle M. Le Beau,John R. Yates,Lara G. Hays,William F. Morgan,William F. Morgan,John H.J. Petrini +10 more
TL;DR: The isolated p95 gene encoding p95, a member of the hMre11/hRad50 double-strand break repair complex, reveals a direct molecular link between DSB repair and cell cycle checkpoint functions in NBS.
Journal ArticleDOI
Nibrin, a Novel DNA Double-Strand Break Repair Protein, Is Mutated in Nijmegen Breakage Syndrome
Raymonda Varon,Christine S. Vissinga,Matthias Platzer,Karen M. Cerosaletti,Krystyna H. Chrzanowska,Kathrin Saar,Georg Beckmann,Eva Seemanova,Paul R. Cooper,Norma J. Nowak,Markus Stumm,Corry M.R. Weemaes,Richard A. Gatti,Richard K. Wilson,Martin Digweed,André Rosenthal,Karl Sperling,Patrick Concannon,André Reis +18 more
TL;DR: The positional cloning of a gene encoding a novel protein, nibrin, which contains two modules found in cell cycle checkpoint proteins, a forkhead-associated domain adjacent to a breast cancer carboxy-terminal domain and a truncating 5 bp deletion are described.
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Nibrin, a Novel DNA Double-Strand Break Repair Protein, Is Mutated in Nijmegen Breakage Syndrome
Raymonda Varon,Christine S. Vissinga,Matthias Platzer,Karen M. Cerosaletti,Krystyna H. Chrzanowska,Kathrin Saar,Georg Beckmann,Eva Seemanova,Paul R. Cooper,Norma J. Nowak,Markus Stumm,Corry M.R. Weemaes,Richard A. Gatti,Richard K. Wilson,Martin Digweed,André Rosenthal,Karl Sperling,Patrick Concannon,André Reis +18 more