Interaction of Nucleotide Excision Repair Protein XPC-RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster.
The combined action of reactive metabolites of benzo[a]pyrene (B[a]P) and oxidative stress can lead to cluster-type DNA damage that includes both a bulky lesion and an apurinic/apyrimidinic (AP) site, which are repaired by the nucleotide and base excision repair mechanisms - NER and BER, respectively. Interaction of NER protein XPC-RAD23B providing primary damage recognition with DNA duplexes containing a B[a]P-derived residue linked to the exocyclic amino group of a guanine (BPDE-N(2)-dG) in the central position of one strand and AP site in different positions of the other strand was analyzed. It was found that XPC-RAD23B crosslinks to DNA containing (+)-trans-BPDE-N(2)-dG more effectively than to DNA containing cis-isomer, independently of the AP site position in the opposite strand; protein affinity to DNA containing one of the BPDE-N(2)-dG isomers depends on the AP site position in the opposite strand. The influence of XPC-RAD23B on hydrolysis of an AP site clustered with BPDE-N(2)-dG catalyzed by the apurinic/apyrimidinic endonuclease 1 (APE1) was examined. XPC-RAD23B was shown to stimulate the endonuclease and inhibit the 3'-5' exonuclease activity of APE1. These data demonstrate the possibility of cooperation of two proteins belonging to different DNA repair systems in the repair of cluster-type DNA damage.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. nadyarec@niboch.nsc.ru.
L V
LV
Starostenko
E A
EA
Maltseva
N A
NA
Lebedeva
P E
PE
Pestryakov
O I
OI
Lavrik
N I
NI
Rechkunova
D000345:Affinity Labels; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification
D000345:Affinity Labels; D018736:DNA Adducts; D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; D011994:Recombinant Proteins; C056612:benzo(a)pyrene-DNA adduct; C086984:XPC protein, human; D001564:Benzo(a)pyrene; D004247:DNA; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D045643:DNA Repair Enzymes