Repair of DNA lesions in chromosomal DNA impact of chromatin structure and Cockayne syndrome proteins.
Decondensation of chromatin is essential to facilitate access to DNA metabolizing processes such as transcription and DNA repair. Disruption of histone-DNA contacts by histone modification or by ATP dependent chromatin remodelling allows DNA-binding proteins to compete with histones for DNA. The efficiency of global genome nucleotide excision repair (GGR) that removes a variety of helix distorting DNA lesions is known to be affected by chromatin structure most notably demonstrated by the slow repair of heterochromatin. In addition, the efficiency of GGR to repair lesions in transcriptionally active genes requires functional CSA and B proteins. We found that repair of UV-photolesions in both strands of the active adenosine deaminase gene was delayed in CS cells when compared to normal human fibroblasts. We suggest that the lack of transcription recovery characteristic for CS cells exposed to DNA damaging agents, might lead to changes in the chromatin structure of active genes, causing less efficient repair of lesions in these genes when compared to normal cells.
Fousteri
Maria
M
Department of Toxicogenetics, Leiden University Medical Centre, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands.
van Hoffen
Anneke
A
Vargova
Hana
H
Mullenders
Leon H F
LH
D002843:Chromatin / Q000235:genetics* / Q000502:physiology; D002877:Chromosomes, Human / Q000235:genetics*; D003057:Cockayne Syndrome / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D006801:Humans
D002843:Chromatin; D004247:DNA