The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair

Research output: Contribution to journal › Journal article › Research › peer-review

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The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair. / González-Corrochano, Rocío; Ruiz, Federico M; Taylor, Nicholas M I; Huecas, Sonia; Drakulic, Srdja; Spínola-Amilibia, Mercedes; Fernández-Tornero, Carlos.

In: Nucleic Acids Research, 21.08.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

González-Corrochano, R, Ruiz, FM, Taylor, NMI, Huecas, S, Drakulic, S, Spínola-Amilibia, M & Fernández-Tornero, C 2020, 'The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair', Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa688

APA

González-Corrochano, R., Ruiz, F. M., Taylor, N. M. I., Huecas, S., Drakulic, S., Spínola-Amilibia, M., & Fernández-Tornero, C. (2020). The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair. Nucleic Acids Research. https://doi.org/10.1093/nar/gkaa688

Vancouver

González-Corrochano R, Ruiz FM, Taylor NMI, Huecas S, Drakulic S, Spínola-Amilibia M et al. The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair. Nucleic Acids Research. 2020 Aug 21. https://doi.org/10.1093/nar/gkaa688

Author

González-Corrochano, Rocío ; Ruiz, Federico M ; Taylor, Nicholas M I ; Huecas, Sonia ; Drakulic, Srdja ; Spínola-Amilibia, Mercedes ; Fernández-Tornero, Carlos. / The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair. In: Nucleic Acids Research. 2020.

Bibtex

@article{42efc77574004dcbb569a6c0001e1d7d,
title = "The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair",
abstract = "Nucleotide excision repair (NER) is an essential pathway to remove bulky lesions affecting one strand of DNA. Defects in components of this repair system are at the ground of genetic diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The XP complementation group G (XPG) endonuclease cleaves the damaged DNA strand on the 3' side of the lesion coordinated with DNA re-synthesis. Here, we determined crystal structures of the XPG nuclease domain in the absence and presence of DNA. The overall fold exhibits similarities to other flap endonucleases but XPG harbors a dynamic helical arch that is uniquely oriented and defines a gateway. DNA binding through a helix-2-turn-helix motif, assisted by one flanking α-helix on each side, shows high plasticity, which is likely relevant for DNA scanning. A positively-charged canyon defined by the hydrophobic wedge and β-pin motifs provides an additional DNA-binding surface. Mutational analysis identifies helical arch residues that play critical roles in XPG function. A model for XPG participation in NER is proposed. Our structures and biochemical data represent a valuable tool to understand the atomic ground of XP and CS, and constitute a starting point for potential therapeutic applications.",
author = "Roc{\'i}o Gonz{\'a}lez-Corrochano and Ruiz, {Federico M} and Taylor, {Nicholas M I} and Sonia Huecas and Srdja Drakulic and Mercedes Sp{\'i}nola-Amilibia and Carlos Fern{\'a}ndez-Tornero",
note = "{\textcopyright} The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2020",
month = aug,
day = "21",
doi = "10.1093/nar/gkaa688",
language = "English",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - The crystal structure of human XPG, the xeroderma pigmentosum group G endonuclease, provides insight into nucleotide excision DNA repair

AU - González-Corrochano, Rocío

AU - Ruiz, Federico M

AU - Taylor, Nicholas M I

AU - Huecas, Sonia

AU - Drakulic, Srdja

AU - Spínola-Amilibia, Mercedes

AU - Fernández-Tornero, Carlos

N1 - © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2020/8/21

Y1 - 2020/8/21

N2 - Nucleotide excision repair (NER) is an essential pathway to remove bulky lesions affecting one strand of DNA. Defects in components of this repair system are at the ground of genetic diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The XP complementation group G (XPG) endonuclease cleaves the damaged DNA strand on the 3' side of the lesion coordinated with DNA re-synthesis. Here, we determined crystal structures of the XPG nuclease domain in the absence and presence of DNA. The overall fold exhibits similarities to other flap endonucleases but XPG harbors a dynamic helical arch that is uniquely oriented and defines a gateway. DNA binding through a helix-2-turn-helix motif, assisted by one flanking α-helix on each side, shows high plasticity, which is likely relevant for DNA scanning. A positively-charged canyon defined by the hydrophobic wedge and β-pin motifs provides an additional DNA-binding surface. Mutational analysis identifies helical arch residues that play critical roles in XPG function. A model for XPG participation in NER is proposed. Our structures and biochemical data represent a valuable tool to understand the atomic ground of XP and CS, and constitute a starting point for potential therapeutic applications.

AB - Nucleotide excision repair (NER) is an essential pathway to remove bulky lesions affecting one strand of DNA. Defects in components of this repair system are at the ground of genetic diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS). The XP complementation group G (XPG) endonuclease cleaves the damaged DNA strand on the 3' side of the lesion coordinated with DNA re-synthesis. Here, we determined crystal structures of the XPG nuclease domain in the absence and presence of DNA. The overall fold exhibits similarities to other flap endonucleases but XPG harbors a dynamic helical arch that is uniquely oriented and defines a gateway. DNA binding through a helix-2-turn-helix motif, assisted by one flanking α-helix on each side, shows high plasticity, which is likely relevant for DNA scanning. A positively-charged canyon defined by the hydrophobic wedge and β-pin motifs provides an additional DNA-binding surface. Mutational analysis identifies helical arch residues that play critical roles in XPG function. A model for XPG participation in NER is proposed. Our structures and biochemical data represent a valuable tool to understand the atomic ground of XP and CS, and constitute a starting point for potential therapeutic applications.

U2 - 10.1093/nar/gkaa688

DO - 10.1093/nar/gkaa688

M3 - Journal article

C2 - 32821917

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

ER -

ID: 248766854