IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v449y2007i7162d10.1038_nature06155.html
   My bibliography  Save this article

Recognition of DNA damage by the Rad4 nucleotide excision repair protein

Author

Listed:
  • Jung-Hyun Min

    (Structural Biology Program and,)

  • Nikola P. Pavletich

    (Structural Biology Program and,
    Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA)

Abstract

Mutations in the nucleotide excision repair (NER) pathway can cause the xeroderma pigmentosum skin cancer predisposition syndrome. NER lesions are limited to one DNA strand, but otherwise they are chemically and structurally diverse, being caused by a wide variety of genotoxic chemicals and ultraviolet radiation. The xeroderma pigmentosum C (XPC) protein has a central role in initiating global-genome NER by recognizing the lesion and recruiting downstream factors. Here we present the crystal structure of the yeast XPC orthologue Rad4 bound to DNA containing a cyclobutane pyrimidine dimer (CPD) lesion. The structure shows that Rad4 inserts a β-hairpin through the DNA duplex, causing the two damaged base pairs to flip out of the double helix. The expelled nucleotides of the undamaged strand are recognized by Rad4, whereas the two CPD-linked nucleotides become disordered. These findings indicate that the lesions recognized by Rad4/XPC thermodynamically destabilize the Watson–Crick double helix in a manner that facilitates the flipping-out of two base pairs.

Suggested Citation

  • Jung-Hyun Min & Nikola P. Pavletich, 2007. "Recognition of DNA damage by the Rad4 nucleotide excision repair protein," Nature, Nature, vol. 449(7162), pages 570-575, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7162:d:10.1038_nature06155
    DOI: 10.1038/nature06155
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature06155
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature06155?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. In-Ja L. Byeon & Guillermo Calero & Ying Wu & Chang H. Byeon & Jinwon Jung & Maria DeLucia & Xiaohong Zhou & Simon Weiss & Jinwoo Ahn & Caili Hao & Jacek Skowronski & Angela M. Gronenborn, 2021. "Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Charlotte Blessing & Katja Apelt & Diana Heuvel & Claudia Gonzalez-Leal & Magdalena B. Rother & Melanie Woude & Román González-Prieto & Adi Yifrach & Avital Parnas & Rashmi G. Shah & Tia Tyrsett Kuo &, 2022. "XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Benjamin Hilton & Sathyaraj Gopal & Lifang Xu & Sharmistha Mazumder & Phillip R Musich & Bongsup P Cho & Yue Zou, 2016. "Dissociation Dynamics of XPC-RAD23B from Damaged DNA Is a Determining Factor of NER Efficiency," PLOS ONE, Public Library of Science, vol. 11(6), pages 1-21, June.
    4. Jina Yu & Chunli Yan & Thomas Dodd & Chi-Lin Tsai & John A. Tainer & Susan E. Tsutakawa & Ivaylo Ivanov, 2023. "Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Corina Maritz & Reihaneh Khaleghi & Michelle N. Yancoskie & Sarah Diethelm & Sonja Brülisauer & Natalia Santos Ferreira & Yang Jiang & Shana J. Sturla & Hanspeter Naegeli, 2023. "ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:449:y:2007:i:7162:d:10.1038_nature06155. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.