Nucleotide excision repair and homologous recombination systems commit differentially to the repair of DNA-protein crosslinks.
DNA-protein crosslinks (DPCs)-where proteins are covalently trapped on the DNA strand-block the progression of replication and transcription machineries and hence hamper the faithful transfer of genetic information. However, the repair mechanism of DPCs remains largely elusive. Here we have analyzed the roles of nucleotide excision repair (NER) and homologous recombination (HR) in the repair of DPCs both in vitro and in vivo using a bacterial system. Several lines of biochemical and genetic evidence show that both NER and HR commit to the repair or tolerance of DPCs, but differentially. NER repairs DPCs with crosslinked proteins of sizes less than 12-14 kDa, whereas oversized DPCs are processed exclusively by RecBCD-dependent HR. These results highlight how NER and HR are coordinated when cells need to deal with unusually bulky DNA lesions such as DPCs.
Nakano
Toshiaki
T
Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan.
Morishita
Soh
S
Katafuchi
Atsushi
A
Matsubara
Mayumi
M
Horikawa
Yusuke
Y
Terato
Hiroaki
H
Salem
Amir M H
AM
Izumi
Shunsuke
S
Pack
Seung Pil
SP
Makino
Keisuke
K
Ide
Hiroshi
H
D000818:Animals; D001374:Azacitidine / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D003432:Cross-Linking Reagents / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004261:DNA Replication; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D043211:Exodeoxyribonuclease V / Q000235:genetics / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D006801:Humans; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic
D003432:Cross-Linking Reagents; D029968:Escherichia coli Proteins; C071446:RecG protein, E coli; D005557:Formaldehyde; D004247:DNA; D004706:Endodeoxyribonucleases; D043211:Exodeoxyribonuclease V; C036385:endodeoxyribonuclease uvrABC; C071059:Holliday junction DNA helicase, E coli; D004265:DNA Helicases; D001374:Azacitidine