Endonucleases

Publication Title: 
Nature

XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer-prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF mutation leading to profound crosslink sensitivity and dramatic progeroid symptoms. It is not known how unrepaired DNA damage accelerates ageing or its relevance to natural ageing. Here we show a highly significant correlation between the liver transcriptome of old mice and a mouse model of this progeroid syndrome.

Author(s): 
Niedernhofer, Laura J.
Garinis, George A.
Raams, Anja
Lalai, Astrid S.
Robinson, Andria Rasile
Appeldoorn, Esther
Odijk, Hanny
Oostendorp, Roos
Ahmad, Anwaar
van Leeuwen, Wibeke
Theil, Arjan F.
Vermeulen, Wim
van der Horst, Gijsbertus T. J.
Meinecke, Peter
Kleijer, Wim J.
Vijg, Jan
Jaspers, Nicolaas G. J.
Hoeijmakers, Jan H. J.
Publication Title: 
Nucleic Acids Research

We examined structural properties of poly d(C4A2).d(T2G4), the telomeric DNA sequence of the ciliated protozoan Tetrahymena. Under conditions of high negative supercoiling, poly d(C4A2).d(T2G4) inserted in a circular plasmid vector was preferentially sensitive to digestion with S1 nuclease. Only the C4A2 strand was sensitive to first-strand S1 cutting, with a markedly skewed pattern of hypersensitive sites in tracts of either 46 or 7 tandem repeats.

Author(s): 
Budarf, M.
Blackburn, E.
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