The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[a]pyrenyl-DNA lesions. - Archive ouverte HAL Access content directly
Journal Articles EMBO Journal Year : 2007

The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[a]pyrenyl-DNA lesions.

Konstantin Kropachev
  • Function : Author
Marina Kolbanovskiy
  • Function : Author
Alexander Kolbanovskiy
  • Function : Author
Angels Tapias
  • Function : Author
Yuqin Cai
  • Function : Author
Suse Broyde
  • Function : Author
Nicholas E Geacintov
  • Function : Author

Abstract

Benzo[a]pyrene (B[a]P), a known environmental pollutant and tobacco smoke carcinogen, is metabolically activated to highly tumorigenic B[a]P diol epoxide derivatives that predominantly form N(2)-guanine adducts in cellular DNA. Although nucleotide excision repair (NER) is an important cellular defense mechanism, the molecular basis of recognition of these bulky lesions is poorly understood. In order to investigate the effects of DNA adduct structure on NER, three stereoisomeric and conformationally different B[a]P-N(2)-dG lesions were site specifically incorporated into identical 135-mer duplexes and their response to purified NER factors was investigated. Using a permanganate footprinting assay, the NER lesion recognition factor XPC/HR23B exhibits, in each case, remarkably different patterns of helix opening that is also markedly distinct in the case of an intra-strand crosslinked cisplatin adduct. The different extents of helix distortions, as well as differences in the overall binding of XPC/HR23B to double-stranded DNA containing either of the three stereoisomeric B[a]P-N(2)-dG lesions, are correlated with dual incisions catalyzed by a reconstituted incision system of six purified NER factors, and by the full NER apparatus in cell-free nuclear extracts.

Dates and versions

hal-00189396 , version 1 (20-11-2007)

Identifiers

Cite

Vincent Mocquet, Konstantin Kropachev, Marina Kolbanovskiy, Alexander Kolbanovskiy, Angels Tapias, et al.. The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[a]pyrenyl-DNA lesions.. EMBO Journal, 2007, 26 (12), pp.2923-32. ⟨10.1038/sj.emboj.7601730⟩. ⟨hal-00189396⟩
14 View
0 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More