Clustered DNA lesions containing 5-formyluracil and AP site: repair via the BER system.
Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1-2 helical turns (clustered lesion). Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site) composed of the clustered lesion with 5-formyluracil (5-foU) by the base excision repair (BER) proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1) decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process.
Laboratory of Bioorganic chemistry of Enzymes, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk, Russia.
Ekaterina A
EA
Belousova
Inna A
IA
Vasil'eva
Nina A
NA
Moor
Timofey S
TS
Zatsepin
Tatiana S
TS
Oretskaya
Olga I
OI
Lavrik
D001483:Base Sequence; D055162:Biocatalysis; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D053837:DNA Cleavage; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives* / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D000076105:X-ray Repair Cross Complementing Protein 1; C007777:5-formyluracil; D014498:Uracil; D004247:DNA; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase