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

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

Stable Identifier

R-HSA-5690996

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

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

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
19941824	Two-step recognition of DNA damage for mammalian nucleotide excision repair: Directional binding of the XPC complex and DNA strand scanning Akagi, J, Iwai, S, Sugasawa, K, Hanaoka, F, Nishi, R	Mol. Cell	2009
20876134	Strand- and site-specific DNA lesion demarcation by the xeroderma pigmentosum group D helicase Naegeli, H, Kaczmarek, N, Mathieu, N	Proc. Natl. Acad. Sci. U.S.A.	2010
19713942	Molecular insights into the recruitment of TFIIH to sites of DNA damage Zhovmer, A, Oksenych, V, Coin, F, Egly, JM, Bernardes de Jesus, B	EMBO J.	2009
17466626	Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair Oksenych, V, Coin, F, Egly, JM	Mol. Cell	2007
23352696	DNA quality control by a lesion sensor pocket of the xeroderma pigmentosum group D helicase subunit of TFIIH Naegeli, H, Luch, A, Kaczmarek, N, Rüthemann, P, Mathieu, N	Curr. Biol.	2013
16491090	Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair Naegeli, H, Dip, R, Schuler, B, Camenisch, U, Schumacher, SB	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 Eker, AP, Winkler, GS, de Laat, WL, Sugasawa, K, Hoeijmakers, JH	Biochemistry	2001
22081108	Functional and structural studies of the nucleotide excision repair helicase XPD suggest a polarity for DNA translocation Michels, G, Wolski, SC, Kuper, J, Kisker, C	EMBO J.	2012