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Updated: Jun 8, 2026

Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
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Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method

Published on: May 2, 2025

Human KIAA1018/FAN1 localizes to stalled replication forks via its ubiquitin-binding domain

Robert D Shereda1, Yuka Machida, Yuichi J Machida

  • 1Division of Oncology Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA.

Cell Cycle (Georgetown, Tex.)
|October 12, 2010
PubMed

Insights

FAN1 is a newly identified nuclear protein crucial for genome stability. It localizes to DNA damage sites and its absence increases sensitivity to DNA crosslinking agents, highlighting its role in genome maintenance.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Genome maintenance pathways are essential for correcting DNA aberrations.
  • Nucleases play a critical role in DNA repair by degrading damaged or obstructive DNA.
  • The function of the putative nuclease KIAA1018/FAN1 was previously unreported.

Purpose of the Study:

  • To characterize the novel nuclease KIAA1018/FAN1.
  • To investigate the role of FAN1 in DNA damage response and genome stability.

Main Methods:

  • Protein domain analysis (UBZ, endonuclease-like fold).
  • Cellular localization studies (nuclear, DNA-damage-induced foci, RPA colocalization).
  • Functional assays (RNA interference for knockdown, sensitivity to interstrand crosslinking agents).

Main Results:

  • FAN1 is a nuclear protein that forms DNA-damage-induced foci at stalled replication forks.
  • FAN1's localization to damage sites depends on its ubiquitin-binding zinc finger (UBZ) domain.
  • FAN1 knockdown results in increased sensitivity to interstrand crosslinking agents and chromosomal abnormalities.

Conclusions:

  • FAN1 is a novel nuclease involved in genome maintenance.
  • FAN1 plays a significant role in responding to DNA damage and maintaining genome stability.
  • FAN1 represents a new target for understanding and potentially treating diseases related to genomic instability.

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