Regulation of translocation polarity by helicase domain 1 in SF2B helicases

Pugh, Robert A.; Wu, Colin G.; Spies, Maria

doi:10.1038/emboj.2011.412

Cited by 63 publications

(102 citation statements)

References 38 publications

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“…In support of our model, recent studies on the entire reconstituted human TFIIH complex also suggested recognition of strongly helix-distorting cisplatin as well as Cy3 adducts on the translocated strand (28). Based on crystallographic and biochemical data in combination with mutational analyses, a structural model has been suggested of how XPD interacts with DNA to recognize lesions (10,11,42). In this model, DNA interactions with amino acid residues along a channel in XPD direct the translocated ssDNA through a pore in the enzyme (see also below).…”

Section: Uvrb and Xpd Helicase Activities Are Activated By Proteinmentioning

confidence: 64%

Conservation and Divergence in Nucleotide Excision Repair Lesion Recognition

Wirth

Gross

Roth

et al. 2016

Journal of Biological Chemistry

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Nucleotide excision repair is an important and highly conserved DNA repair mechanism with an exceptionally large range of chemically and structurally unrelated targets. Lesion verification is believed to be achieved by the helicases UvrB and XPD in the prokaryotic and eukaryotic processes, respectively. Using single molecule atomic force microscopy analyses, we demonstrate that UvrB and XPD are able to load onto DNA and pursue lesion verification in the absence of the initial lesion detection proteins. Interestingly, our studies show different lesion recognition strategies for the two functionally homologous helicases, as apparent from their distinct DNA strand preferences, which can be rationalized from the different structural features and interactions with other nucleotide excision repair protein factors of the two enzymes. Nucleotide excision repair (NER)4 is an important DNA repair mechanism with a large range of chemically and structurally unrelated targets. Examples range from bulky DNA adducts to interstrand DNA cross-links caused by antitumor drugs (1-3). In humans, NER is the only repair system for the removal of UV irradiation-induced photoproducts such as the intrastrand cross-linking cyclobutane-pyrimidine dimers (CPDs), and dysfunctional NER is responsible for severe diseases, including xeroderma pigmentosum (XP) (1-3).The mechanism of NER is highly conserved between organisms. In bacteria, NER involves the proteins UvrA, UvrB, and UvrC. In the current model of prokaryotic NER, a hetero-tetrameric complex of UvrA and UvrB (UvrA 2 B 2 ) scans the DNA for lesions. When a lesion is encountered, initial lesion sensing by a dimer of UvrA is based on detection of DNA distortion. Conformational changes in the UvrA 2 B 2 complex result in an unwinding and opening of dsDNA around the lesion, providing an unpaired (bubble) region likely required by UvrB to thread onto one of the ssDNA strands. The helicase UvrB is believed to verify the presence of a lesion by insertion of a ␤-hairpin via interactions with residues at the base of the hairpin (2). Upon lesion verification by UvrB, UvrA dissociates from the complex, and ATP re-binding by UvrB results in the formation of the lesion-specific UvrB-DNA complex, which recruits the NER endonuclease UvrC (UvrBC complex). UvrC carries out two incisions on either side of the lesion. The 12-13-nucleotide (nt)-long ssDNA stretch (2) containing the lesion can then be removed together with the endonuclease by the helicase UvrD, and the resulting gap is filled and sealed by DNA polymerase I and ligase.Eukaryotic NER encompasses a total of ϳ30 proteins, including the xeroderma pigmentosum group proteins (XPA-XPG). Repair can either be initiated by a stalled RNA polymerase in transcription-coupled NER or via global genome NER. In global genome NER, upon initial detection of short destabilized DNA structures by the CEN2-XPC-HR23B complex, the ATPase/ helicase XPB, which is part of the 10-subunit transcription factor IIH (TFIIH) complex, then directly interacts with XPC (4) and...

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Section: Uvrb and Xpd Helicase Activities Are Activated By Proteinmentioning

confidence: 64%

Conservation and Divergence in Nucleotide Excision Repair Lesion Recognition

Wirth

Gross

Roth

et al. 2016

Journal of Biological Chemistry

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“…Several lines of evidence lead to the currently accepted hypothesis that the lesions are initially recognized by XPC with the help of UV-DDB (UV DNA damage binding protein) for cyclobutane pyrimidine dimer (CPD) lesions (17)(18)(19)(20) followed by damage verification by XPD/TFIIH (21)(22)(23)(24), XPA, and XPG (3) to finally assemble to the preincision complex (3,(25)(26)(27). This step seems to involve recruitment of the XPA protein, which is one of the proteins essential for both GG-NER and TC-NER (28).…”

mentioning

confidence: 99%

Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA)

Koch

Kuper

Gasteiger

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Nucleotide excision repair (NER) is responsible for the removal of a large variety of structurally diverse DNA lesions. Mutations of the involved proteins cause the xeroderma pigmentosum (XP) cancer predisposition syndrome. Although the general mechanism of the NER process is well studied, the function of the XPA protein, which is of central importance for successful NER, has remained enigmatic. It is known, that XPA binds kinked DNA structures and that it interacts also with DNA duplexes containing certain lesions, but the mechanism of interactions is unknown. Here we present two crystal structures of the DNA binding domain (DBD) of the yeast XPA homolog Rad14 bound to DNA with either a cisplatin lesion (1,2-GG) or an acetylaminofluorene adduct (AAF-dG). In the structures, we see that two Rad14 molecules bind to the duplex, which induces DNA melting of the duplex remote from the lesion. Each monomer interrogates the duplex with a β-hairpin, which creates a 13mer duplex recognition motif additionally characterized by a sharp 70°DNA kink at the position of the lesion. Although the 1,2-GG lesion stabilizes the kink due to the covalent fixation of the crosslinked dG bases at a 90°angle, the AAF-dG fully intercalates into the duplex to stabilize the kinked structure.

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“…The iron-sulfur and arch domains together with helicase domain 1 comprise a narrow pore with ϳ1-nm diameter (8,9). In addition, the crystal structure of taXPD in complex with a short stretch of ssDNA, as well as reverse footprinting analysis, have led to a model of the possible path of the DNA across the enzyme (11,18). In this model, the DNA threads through the protein pore and is in close proximity to the iron-sulfur cluster, consistent with a proposed role of such clusters in DNA damage investigation (19 -23) and the recent identification of a dedicated lesion recognition pocket near the pore (12).…”

mentioning

confidence: 99%

Strand-specific Recognition of DNA Damages by XPD Provides Insights into Nucleotide Excision Repair Substrate Versatility

Buechner

Heil

Michels

et al. 2014

Journal of Biological Chemistry

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Background: XPD is important for DNA lesion recognition by the nucleotide excision repair (NER) system. Results: Dependent on the lesion type, XPD recognizes lesions either on the protein-translocated or on the nontranslocated DNA strand. Conclusion: XPD employs different recognition strategies for different types of damage. Significance: Different lesion-specific recognition approaches may enhance the remarkably broad target spectrum of NER.

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Regulation of translocation polarity by helicase domain 1 in SF2B helicases

Cited by 63 publications

References 38 publications

Conservation and Divergence in Nucleotide Excision Repair Lesion Recognition

Conservation and Divergence in Nucleotide Excision Repair Lesion Recognition

Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA)

Strand-specific Recognition of DNA Damages by XPD Provides Insights into Nucleotide Excision Repair Substrate Versatility

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