Formation of the pre-incision complex in GG-NER

Stable Identifier
R-HSA-5689317
Type
Reaction
Species
Homo sapiens
Compartment
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Summation

Once an open bubble structure is generated in damaged dsDNA through a DNA helicase activity of the TFIIH complex, the RPA heterotrimer composed of RPA1, RPA2 and RPA3, coats the undamaged single strand DNA (ssDNA) (de Laat et al. 1998), thereby protecting it from incision and enabling the correct positioning of the NER endonucleases. The interaction of RPA with XPA facilitates RPA recruitment to the global genome nucleotide excision repair (GG-NER) site (He et al. 1995, Ikegami et al. 1998). A DNA endonuclease ERCC5 (XPG) is recruited to the GG-NER site, 3' to the DNA damage, through its interaction with the TFIIH complex (Dunand-Sauthier et al. 2005, Zotter et al. 2006, Ito et al. 2007) and the RPA heterotrimer (de Laat et al. 1998).

Literature References
PubMed ID Title Journal Year
7700386 RPA involvement in the damage-recognition and incision steps of nucleotide excision repair

He, Z, Henricksen, LA, Wold, MS, Ingles, CJ

Nature 1995
9716411 DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair

de Laat, WL, Appeldoorn, E, Sugasawa, K, Weterings, E, Jaspers, NG, Hoeijmakers, JH

Genes Dev. 1998
17000769 Recruitment of the nucleotide excision repair endonuclease XPG to sites of UV-induced dna damage depends on functional TFIIH

Zotter, A, Luijsterburg, MS, Warmerdam, DO, Ibrahim, S, Nigg, A, van Cappellen, WA, Hoeijmakers, JH, van Driel, R, Vermeulen, W, Houtsmuller, AB

Mol. Cell. Biol. 2006
9699634 Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA

Ikegami, T, Kuraoka, I, Saijo, M, Kodo, N, Kyogoku, Y, Morikawa, K, Tanaka, K, Shirakawa, M

Nat. Struct. Biol. 1998
17466625 XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients

Ito, S, Kuraoka, I, Chymkowitch, P, Compe, E, Takedachi, A, Ishigami, C, Coin, F, Egly, JM, Tanaka, K

Mol. Cell 2007
15590680 The spacer region of XPG mediates recruitment to nucleotide excision repair complexes and determines substrate specificity

Dunand-Sauthier, I, Hohl, M, Thorel, F, Jaquier-Gubler, P, Clarkson, SG, Schärer, OD

J. Biol. Chem. 2005
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