[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleEEPD1 evolved a unique DNA clamping dimer protecting reversed replication forks.
Journal, issue, pagesNucleic Acids Res, Vol. 54, Issue 5, Year 2026
Publish dateFeb 24, 2026
AuthorsRunze Shen / Altaf H Sarker / Yue Chen / Min Liu / Sunetra Roy / Andrew S Arvai / Albino Bacolla / Zamal Ahmed / Panagiotis Katsonis / Michal Hammel / Isao Kuraoka / Miaw-Sheue Tsai / Corydon Irie / Lukas Webb / Olivier Lichtarge / Chi-Lin Tsai / Susan E Tsutakawa / Katharina Schlacher / John A Tainer /
PubMed AbstractExonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 ...Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an unprecedented tryptophan handshake dimer, conserved interface di-Trp-Pro pocket, and adjustable "wrist" enabling an open-closed conformational switch. EEPD1 dimer cooperatively binds complex dsDNA replication fork intermediates but alone lacks nuclease activity due to loss of key EEP catalytic residues during Metazoan evolution and atmospheric oxygen buildup. Instead, EEPD1 prevents nucleolytic degradation of reversed replication forks by MRE11. Furthermore, cancer bioinformatics support oxidative damage-dependent EEPD1 association as a significant modulator of overall patient survival. Collective findings uncover unexpected EEP dimer and fork protection function in clamping, not cleaving, reversed replication forks for metazoan oxidative stress responses controlling genome stability and cancer outcomes.
External linksNucleic Acids Res / PubMed:41830330 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.59 - 3.6 Å
Structure data

72976

9yi2

EMDB-72976, PDB-9yi2:
Human EEPD1 EEP domain dimer
Method: EM (single particle) / Resolution: 3.6 Å

PDB-9ysf:
Crystal structure of EEPD1 EEP domain dimer with Mg(II)
Method: X-RAY DIFFRACTION / Resolution: 1.59 Å

PDB-9yxy:
Crystal structure of EEPD1 EEP domain dimer at pH 5.5
Method: X-RAY DIFFRACTION / Resolution: 2 Å

Chemicals

ChemComp-EDO:
1,2-ETHANEDIOL

ChemComp-TRS:
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / pH buffer*YM

ChemComp-MG:
Unknown entry

ChemComp-CL:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-GOL:
GLYCEROL

ChemComp-IMD:
IMIDAZOLE

Source
  • homo sapiens (human)
KeywordsDNA BINDING PROTEIN / Endonuclease/Exonuclease/Phosphatase Fold / dimerization / helix-hairpin-helix domains / replication stress response

+
About Yorodumi Papers

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more