Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases

@article{Redondo2008MolecularBO,
  title={Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases},
  author={Pilar Redondo and Jes{\'u}s Prieto and In{\'e}s G. Mu{\~n}oz and Andreu Alib{\'e}s and François Stricher and Luis Serrano and J P Cabaniols and Fayza Daboussi and Sylvain Arnould and Christophe Perez and Philippe Duchateau and Fr{\'e}d{\'e}ric P{\^a}ques and Francisco J. Blanco and Guillermo Montoya},
  journal={Nature},
  year={2008},
  volume={456},
  pages={107-111}
}
Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases—such as homing endonucleases, also known as meganucleases—constitutes one possible strategy for repairing DNA lesions. Homing… 

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References

SHOWING 1-10 OF 33 REFERENCES

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro

Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops.

Cancer in xeroderma pigmentosum and related disorders of DNA repair

Nucleotide-excision repair diseases exhibit cancer, complex developmental disorders and neurodegeneration, and complex clinical phenotypes might result from unanticipated effects on other genes and proteins.

Highly efficient endogenous human gene correction using designed zinc-finger nucleases

It is shown that zinc-finger nucleases designed against an X-linked severe combined immune deficiency mutation in the IL2Rγ gene yielded more than 18% gene-modified human cells without selection, raising the possibility of strategies based on zinc- finger nucleases for the treatment of disease.

The C-terminal loop of the homing endonuclease I-CreI is essential for site recognition, DNA binding and cleavage

It is demonstrated that the C-terminal loop of I-CreI endonuclease plays a fundamental role in its catalytic mechanism and suggested this novel site as a region to take into account for engineering new endonucleases with tailored specificity.

A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences

The first artificial HEs whose specificity has been entirely redesigned to cleave a naturally occurring sequence are described, demonstrating that the plasticity of LAGLIDADG endonucleases allows extensive engineering, and provide a general method to create novel endon nucleases with tailored specificities.

An xrcc4 defect or Wortmannin stimulates homologous recombination specifically induced by double-strand breaks in mammalian cells.

A model according to which NHEJ and HR do not simply compete for DSB repair but can act sequentially is suggested: a defect in a late N HEJ step is not a dead end and can make DSB available for subsequent Rad51 recombination complex assembly.

Directed evolution of the site specificity of Cre recombinase

  • S. SantoroP. Schultz
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
A directed evolution strategy is developed that can be used to identify recombinases that recognize variant loxP sites and selectively recombines a novel recombination site and operates at a rate identical to that of wild-type Cre.