The role of double-strand break repair — insights from human genetics

@article{ODriscoll2006TheRO,
  title={The role of double-strand break repair — insights from human genetics},
  author={Mark O’Driscoll and Penny A. Jeggo},
  journal={Nature Reviews Genetics},
  year={2006},
  volume={7},
  pages={45-54}
}
The efficient repair of DNA double-strand breaks is crucial in safeguarding the genomic integrity of organisms. Responses to double-strand breaks include complex signal-transduction, cell-cycle-checkpoint and repair pathways. Defects in these pathways lead to several human disorders with pleiotropic clinical features. Dissection of the molecular basis that underlies the diverse clinical features is enhancing our understanding of the damage-response mechanisms and their role in development, and… Expand
View on Springer
ncbi.nlm.nih.gov
561 Citations
Highly Influential Citations
38
Background Citations
228
Methods Citations
9
Results Citations
3

Figures, Tables, and Topics from this paper

561 Citations

Citation Type

Citation Type

Targeting the Double-Strand DNA Break Repair Pathway as a Therapeutic Strategy
DNA repair pathways are crucial for the maintenance of genome integrity. The pathway that repairs DNA double-strand breaks (DSB) has components involved in both signaling and repairing DNA damage.… Expand
DNA damage response: the players, the network and the role in tumor suppression.
TLDR
This review provides an overview on the molecular events in DNA damage signaling pathway, including cell cycle checkpoint and DNA repair, which contributes to genomic instability and cancer development. Expand
Mouse models of DNA double-strand break repair and neurological disease.
TLDR
The use of mouse models represents an important approach for advancing the understanding of the biology of the DNA damage response in the nervous system and new treatments for neurodegeneration and cancer. Expand
DNA Double Strand Break Repair: Mechanisms and Therapeutic Potential
DNA double strand breaks are widely considered to be the most cytotoxic form of DNA damage. They can be induced by exposure to exogenous agents such as ionizing radiation and topoisomerase poisons… Expand
BRCA2 Function and the Central Nervous System
TLDR
How this study contributes both to the authors' understanding of BRCA2 functions in vivo, and the tissue-specific requirements for DNA repair and damage-signaling pathways is discussed. Expand
RAD18 lives a double life: Its implication in DNA double-strand break repair.
TLDR
It is reviewed how RAD18 carries out these distinct functions in response to different types of DNA lesions, which is an error-free DNA repair pathway that mediates the repair of double-strand breaks (DSBs). Expand
The repair and signaling responses to DNA double-strand breaks.
TLDR
This review overviews the cellular response to DSBs focusing on DNA repair pathways and the interface between them and considers additional events which impact upon these DSB repair pathways, including regulated arrest of cell cycle progression and chromatin architecture alterations. Expand
The ATM-mediated DNA-damage response: taking shape.
  • Y. Shiloh
  • Biology, Medicine
  • Trends in biochemical sciences
  • 2006
TLDR
Genetic, biochemical and structural studies have recently provided insights into the ATM-mediated DSB response, reshaping the view of this signaling pathway while raising new questions. Expand
DNA double-strand break repair: from mechanistic understanding to cancer treatment.
TLDR
This review aims to provide a foundational understanding of how the homologous recombination and non-homologous end joining pathways operate, and to demonstrate how a better understanding of these processes has advanced both the understanding of the underlying causes of cancer and the ability to innovate novel cancer treatment strategies. Expand
The Role of Deubiquitinases in DNA Double-Strand Break Repair
DNA double-strand break (DSB) is a type of the most critical DNA lesions, and if not repaired promptly, it can result in cell death or a wide variety of genetic alterations including genome… Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 126 REFERENCES
The DNA double-strand break response in the nervous system.
TLDR
DNA double-strand breaks (DSBs) require a coordinated molecular response to ensure cellular or organism survival, and appropriate responses to DSBs are critical for the normal development and maintenance of the nervous system. Expand
Molecular views of recombination proteins and their control
  • S. West
  • Biology, Medicine
  • Nature Reviews Molecular Cell Biology
  • 2003
TLDR
The efficient repair of double-strand breaks in DNA is critical for the maintenance of genome stability and cell survival, especially in replicating cells, in which it plays a major role in tumour avoidance. Expand
The cellular response to DNA double-strand breaks: defining the sensors and mediators.
TLDR
This work discusses the possible role of the Mre11 complex as a primary damage sensor and the complex relationship between DNA damage sensors, transducers and mediators and proposed criteria for defining sensor proteins. Expand
The mammalian XRCC genes: their roles in DNA repair and genetic stability.
TLDR
The phenotypic effects of mutation of the XRCC genes, and the current state of the authors' knowledge of their functions are documented. Expand
The DNA damage response: putting checkpoints in perspective
TLDR
The inability to repair DNA damage properly in mammals leads to various disorders and enhanced rates of tumour development, and this work has shown that direct activation of DNA repair networks is needed to correct this problem. Expand
The XRCC genes: expanding roles in DNA double-strand break repair.
TLDR
Confirmation that these responses are likely to contribute to cancer induction and/or progression, is given by studies of humans and mice with XRCC gene disruptions: those affecting NHEJ show increased lymphoid tumours, while those affecting HR lead to breast cancer and perhaps to gynaecological tumours. Expand
Functional links between telomeres and proteins of the DNA-damage response.
TLDR
The current knowledge of both the telomere and the DDR are discussed, and an integrated model for the events associated with the metabolism of DNA ends in these two distinct physiological contexts are proposed. Expand
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
TLDR
BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage. Expand
Impairment of V(D)J recombination in double-strand break repair mutants.
TLDR
Evidence is provided for two distinct nonlymphoid-specific genes that encode factors involved in both DNA repair and V(D)J recombination in cells deficient in DNA repair. Expand
ATM function and telomere stability
TLDR
It has now been demonstrated that mutations in ATM lead to defective telomere maintenance in mammalian cells, and how ATM and telomeres serve as controllers of cellular responses to DNA damage is reviewed. Expand
...
1
2
3
4
5
...