ATP-dependent chromatin remodeling is required for base excision repair in conventional but not in variant H2A.Bbd nucleosomes.
In eukaryotes, base excision repair (BER) is responsible for the repair of oxidatively generated lesions. The mechanism of BER on naked DNA substrates has been studied in detail, but how it operates on chromatin remains unclear. Here we have studied the mechanism of BER by introducing a single 8-oxo-7,8-dihydroguanine (8-oxoG) lesion in the DNA of reconstituted positioned conventional and histone variant H2A.Bbd nucleosomes. We found that 8-oxoguanine DNA glycosylase, apurinic/apyrimidinic endonuclease, and polymerase beta activities were strongly reduced in both types of nucleosomes. In conventional nucleosomes SWI/SNF stimulated the processing of 8-oxoG by each one of the three BER repair factors to efficiencies similar to those for naked DNA. Interestingly, SWI/SNF-induced remodeling, but not mobilization of conventional nucleosomes, was required to achieve this effect. A very weak effect of SWI/SNF on the 8-oxoG BER removal in H2A.Bbd histone variant nucleosomes was observed. The possible implications of our data for the understanding of in vivo mechanisms of BER are discussed.
Menoni
Hervé
H
Laboratoire Joliot-Curie, CNRS-USR3010, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 7, France.
Gasparutto
Didier
D
Hamiche
Ali
A
Cadet
Jean
J
Dimitrov
Stefan
S
Bouvet
Philippe
P
Angelov
Dimitar
D
D000255:Adenosine Triphosphate / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004249:DNA Damage; D018983:DNA Footprinting; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C024829:8-hydroxyguanine; D006147:Guanine; D000255:Adenosine Triphosphate; D019951:DNA Polymerase beta; D043382:DNA-Formamidopyrimidine Glycosylase; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase