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UV damage causes uncontrolled DNA breakage in cells from patients with combined features of XP‐D and Cockayne syndrome
Author(s) -
Berneburg Mark,
Lowe Jillian E.,
Nardo Tiziana,
Araújo Sofia,
Fousteri Maria I.,
Green Michael H.L.,
Krutmann Jean,
Wood Richard D.,
Stefanini Miria,
Lehmann Alan R.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.5.1157
Subject(s) - xeroderma pigmentosum , cockayne syndrome , dna damage , nucleotide excision repair , biology , dna repair , microbiology and biotechnology , dna , plasmid , genetics
Nucleotide excision repair (NER) removes damage from DNA in a tightly regulated multiprotein process. Defects in NER result in three different human disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS). Two cases with the combined features of XP and CS have been assigned to the XP‐D complementation group. Despite their extreme UV sensitivity, these cells appeared to incise their DNA as efficiently as normal cells in response to UV damage. These incisions were, however, uncoupled from the rest of the repair process. Using cell‐free extracts, we were unable to detect any incision activity in the neighbourhood of the damage. When irradiated plasmids were introduced into unirradiated XP‐D/CS cells, the ectopically introduced damage triggered the induction of breaks in the undamaged genomic DNA. XP‐D/CS cells thus have a unique response to sensing UV damage, which results in the introduction of breaks into the DNA at sites distant from the damage. We propose that it is these spurious breaks that are responsible for the extreme UV sensitivity of these cells.