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Human DNA ligase I completely encircles and partially unwinds nicked DNA

Author

Listed:
  • John M. Pascal

    (Harvard Medical School)

  • Patrick J. O'Brien

    (Harvard Medical School
    University of Michigan)

  • Alan E. Tomkinson

    (University of Maryland School of Medicine)

  • Tom Ellenberger

    (Harvard Medical School)

Abstract

The end-joining reaction catalysed by DNA ligases is required by all organisms and serves as the ultimate step of DNA replication, repair and recombination processes. One of three well characterized mammalian DNA ligases, DNA ligase I, joins Okazaki fragments during DNA replication. Here we report the crystal structure of human DNA ligase I (residues 233 to 919) in complex with a nicked, 5′ adenylated DNA intermediate. The structure shows that the enzyme redirects the path of the double helix to expose the nick termini for the strand-joining reaction. It also reveals a unique feature of mammalian ligases: a DNA-binding domain that allows ligase I to encircle its DNA substrate, stabilizes the DNA in a distorted structure, and positions the catalytic core on the nick. Similarities in the toroidal shape and dimensions of DNA ligase I and the proliferating cell nuclear antigen sliding clamp are suggestive of an extensive protein–protein interface that may coordinate the joining of Okazaki fragments.

Suggested Citation

  • John M. Pascal & Patrick J. O'Brien & Alan E. Tomkinson & Tom Ellenberger, 2004. "Human DNA ligase I completely encircles and partially unwinds nicked DNA," Nature, Nature, vol. 432(7016), pages 473-478, November.
    • Handle: RePEc:nat:nature:v:432:y:2004:i:7016:d:10.1038_nature03082
    DOI: 10.1038/nature03082
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    Cited by:

    1. Qun Tang & Mitchell Gulkis & Robert McKenna & Melike Çağlayan, 2022. "Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Kerry Blair & Muhammad Tehseen & Vlad-Stefan Raducanu & Taha Shahid & Claudia Lancey & Fahad Rashid & Ramon Crehuet & Samir M. Hamdan & Alfredo De Biasio, 2022. "Mechanism of human Lig1 regulation by PCNA in Okazaki fragment sealing," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Vlad-Stefan Raducanu & Muhammad Tehseen & Amani Al-Amodi & Luay I. Joudeh & Alfredo Biasio & Samir M. Hamdan, 2022. "Mechanistic investigation of human maturation of Okazaki fragments reveals slow kinetics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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