Interaction of Nucleotide Excision Repair Protein XPC–RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster

---

L. V. Starostenko¹, E. A. Maltseva¹, N. A. Lebedeva^1,2, P. E. Pestryakov¹, O. I. Lavrik^1,2, and N. I. Rechkunova^1,2*

¹Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; fax: + (383) 363-5153; E-mail: nadyarec@niboch.nsc.ru

²Novosibirsk State University, 630090 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received May 20, 2015; Revision received September 27, 2015

---

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-N²-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-N²-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-N²-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-N²-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.

---

KEY WORDS: protein factors of nucleotide excision repair, benzo[a]pyrene derivatives, apurinic/apyrimidinic site, cluster-type DNA damage, affinity labeling, DNA–protein complexes

DOI: 10.1134/S0006297916030056

---