ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA

Stable Identifier
R-HSA-5690996
Type
Reaction [transition]
Species
Homo sapiens
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Two DNA helicases XPB (ERCC3) and XPD (ERCC2), which are part of the TFIIH complex, unwind the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site. The helicase activity of the TFIIH complex is stimulated by the presence of XPA and the XPC:RAD23:CETN2 complex (Winkler et al. 2001). The 5'->3' directed helicase activity of ERCC2 (Kuper et al. 2012) is crucial for unwinding of the distorted dsDNA during nucleotide excision repair (NER) (Coin et al. 2007). The 3'->5' directed DNA helicase ERCC3 contributes to dsDNA unwinding during NER through ATP hydrolysis (Coin et al. 2007). In addition to DNA unwinding, ERCC2 and ERCC3 verify the presence of DNA damage (Oksenych et al. 2009, Mathieu et al. 2010, Mathieu et al. 2013). Verification of DNA damage also involves XPA (Camenisch et al. 2006). The binding site of XPC determines which DNA strand is selected by ERCC2 to verify the presence of lesions (Sugasawa et al. 2009).

Literature References
PubMed ID Title Journal Year
20876134 Strand- and site-specific DNA lesion demarcation by the xeroderma pigmentosum group D helicase

Mathieu, N, Kaczmarek, N, Naegeli, H

Proc. Natl. Acad. Sci. U.S.A. 2010
19941824 Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning

Sugasawa, K, Akagi, J, Nishi, R, Iwai, S, Hanaoka, F

Mol. Cell 2009
19713942 Molecular insights into the recruitment of TFIIH to sites of DNA damage

Oksenych, V, Bernardes de Jesus, B, Zhovmer, A, Egly, JM, Coin, F

EMBO J. 2009
17466626 Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair

Coin, F, Oksenych, V, Egly, JM

Mol. Cell 2007
23352696 DNA quality control by a lesion sensor pocket of the xeroderma pigmentosum group D helicase subunit of TFIIH

Mathieu, N, Kaczmarek, N, RĂ¼themann, P, Luch, A, Naegeli, H

Curr. Biol. 2013
16491090 Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair

Camenisch, U, Dip, R, Schumacher, SB, Schuler, B, Naegeli, H

Nat. Struct. Mol. Biol. 2006
11141066 Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF

Winkler, GS, Sugasawa, K, Eker, AP, de Laat, WL, Hoeijmakers, JH

Biochemistry 2001
22081108 Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation

Kuper, J, Wolski, SC, Michels, G, Kisker, C

EMBO J. 2012
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Catalyst Activity
Title
helicase activity of Ub:XPC:RAD23:CETN2:Distorted dsDNA:PAR-UV-DDB:TFIIH Core:XPA:PAR-PARP1,PAR-PARP2:CHD1L [nucleoplasm]
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