The endless tale of non-homologous end-joining.
Eric Weterings,David J. Chen +1 more
Reads0
Chats0
TLDR
In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented.Abstract:
DNA double-strand breaks (DSBs) are introduced in cells by ionizing radiation and reactive oxygen species. In addition, they are commonly generated during V(D)J recombination, an essential aspect of the developing immune system. Failure to effectively repair these DSBs can result in chromosome breakage, cell death, onset of cancer, and defects in the immune system of higher vertebrates. Fortunately, all mammalian cells possess two enzymatic pathways that mediate the repair of DSBs: homologous recombination and non-homologous end-joining (NHEJ). The NHEJ process utilizes enzymes that capture both ends of the broken DNA molecule, bring them together in a synaptic DNA-protein complex, and finally repair the DNA break. In this review, all the known enzymes that play a role in the NHEJ process are discussed and a working model for the co-operation of these enzymes during DSB repair is presented.read more
Citations
More filters
Journal ArticleDOI
Mechanisms of DNA damage, repair, and mutagenesis.
TL;DR: This introductory review will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.
Journal ArticleDOI
Complex landscapes of somatic rearrangement in human breast cancer genomes.
Philip J. Stephens,David J. McBride,Meng-Lay Lin,Ignacio Varela,Erin Pleasance,Jared T. Simpson,Lucy Stebbings,Catherine Leroy,Sarah Edkins,Laura Mudie,Christopher Greenman,Mingming Jia,Calli Latimer,Jon W. Teague,King Wai Lau,John Burton,Michael A. Quail,Harold Swerdlow,Carol Churcher,Rachael Natrajan,Anieta M. Sieuwerts,John W.M. Martens,Daniel P. Silver,Anita Langerød,Hege G. Russnes,John A. Foekens,Jorge S. Reis-Filho,Laura van 't Veer,Andrea L. Richardson,Anne Lise Børresen-Dale,Peter J. Campbell,P. Andrew Futreal,Michael R. Stratton,Michael R. Stratton +33 more
TL;DR: A paired-end sequencing strategy is used to identify somatic rearrangements in breast cancer genomes and provides a new perspective on cancer genomes, highlighting the diversity of somatic upheavals and their potential contribution to cancer development.
Journal ArticleDOI
ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2.
Andrea Beucher,Julie Birraux,Leopoldine Tchouandong,Olivia Barton,Atsushi Shibata,Sandro Conrad,Aaron A. Goodarzi,Andrea Krempler,Penny A. Jeggo,Markus Löbrich +9 more
TL;DR: It is shown that in G2, as in G1, NHEJ represents the major DSB‐repair pathway whereas HR is only essential for repair of ∼15% of X‐ or γ‐ray‐induced DSBs.
Journal ArticleDOI
Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
TL;DR: It is shown that PARP inhibitor treatment induces phosphorylation of DNA-dependent protein kinase substrates and stimulates error-prone nonhomologous end joining (NHEJ) selectively in HR-deficient cells, and it is indicated that deregulated NHEJ plays a major role in generating the genomic instability and cytotoxicity in HRs treated with PARP inhibitors.
Journal ArticleDOI
DNA double strand break repair via non-homologous end-joining
Anthony J. Davis,David J. Chen +1 more
TL;DR: In this review, interesting new insights are discussed into the mechanism of the NHEJ pathway and the proteins which mediate this repair process and the general role of N HEJ in promoting genomic stability will be discussed.
References
More filters
Journal ArticleDOI
Genome maintenance mechanisms for preventing cancer
TL;DR: This review summarizes the main DNA caretaking systems and their impact on genome stability and carcinogenesis.
Journal ArticleDOI
DNA double-strand breaks: signaling, repair and the cancer connection.
TL;DR: Recent progress is described in understanding of how cells detect and signal the presence and repair of one particularly important form of DNA damage induced by ionizing radiation—the DNA double-strand break (DSB).
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.
Journal ArticleDOI
Chromosomal stability and the DNA double-stranded break connection.
TL;DR: Interactions between both double-stranded break-repair pathways and other cellular processes, such as cell-cycle regulation and replication, are being unveiled.
Journal ArticleDOI
Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair.
TL;DR: The Ku heterodimer (Ku70 and Ku80 subunits) contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway.