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Interaction of nucleotide excision repair factors RPA and XPA with DNA containing bulky photoreactive groups imitating damages

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Abstract

Interaction of nucleotide excision repair factors—replication protein A (RPA) and Xeroderma pigmentosum complementing group A protein (XPA)—with DNA structures containing nucleotides with bulky photoreactive groups imitating damaged nucleotides was investigated. Efficiency of photoaffinity modification of two proteins by photoreactive DNAs varied depending on DNA structure and type of photoreactive group. The secondary structure of DNA and, first of all, the presence of extended single-stranded parts plays a key role in recognition by RPA. However, it was shown that RPA efficiently interacts with DNA duplex containing a bulky substituent at the 5′-end of a nick. XPA was shown to prefer the nicked DNA; however, this protein was cross-linked with approximately equal efficiency by single-stranded and double-stranded DNA containing a bulky substituent inside the strand. XPA seems to be sensitive not only to the structure of DNA double helix, but also to a bulky group incorporated into DNA. The mechanism of damage recognition in the process of nucleotide excision repair is discussed.

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Abbreviations

FAB-dUMP:

5-{[4-(4-azido-2,3,5,6-tetrafluo-robenzoylamino)butyl]-aminocarbonyl-carbamolyl-propyloxymethyl}-2′-deoxyuridine-5′-monophosphate

FAP-dUMP:

5-{N-[N-(4-azido-2,5-difluoro-3-chloropyridin-6-yl)-3-aminopropionyl]-trans-3-aminopropenyl-1}-2′-deoxyuridine-5′-monophosphate

FAP-dCMP:

exo-N-{2-[N-(4-azido-2,5-difluoro-3-chloropyridin-6-yl)-3-aminopropionyl]-amino-ethyl}-2′-deoxycitidine-5′-monophosphate

NER:

nucleotide excision repair

RPA:

replication protein A

XPA:

Xeroderma pigmentosum complementing group A factor

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Correspondence to O. I. Lavrik.

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Original Russian Text © E. A. Maltseva, N. I. Rechkunova, I. O. Petruseva, V. N. Silnikov, W. Vermeulen, O. I. Lavrik, 2006, published in Biokhimiya, 2006, Vol. 71, No. 3, pp. 342–352.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM05-194, December 11, 2005.

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Maltseva, E.A., Rechkunova, N.I., Petruseva, I.O. et al. Interaction of nucleotide excision repair factors RPA and XPA with DNA containing bulky photoreactive groups imitating damages. Biochemistry (Moscow) 71, 270–278 (2006). https://doi.org/10.1134/S0006297906030060

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  • DOI: https://doi.org/10.1134/S0006297906030060

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