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

Robert D. Shereda, Yuka Machida, Yuichi J. Machida

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Genome maintenance pathways correct aberrations in DNA that would be deleterious to the organism. A crucial element of many genome maintenance processes is the ability to degrade DNA that either contains errors or obscures useful substrates for recombination and/or repair by means of nucleases. We have examined a putative nuclease that has heretofore been unreported, KIAA1018/FAN1. This protein contains a predicted ubiquitin-binding zinc finger domain (UBZ) near its N-terminus and an endonuclease-like fold near its C-terminus. Here we describe that FAN1 is a nuclear protein and forms DNA-damage-induced foci, which appear to be at stalled replication forks as denoted by RPA colocalization. Localization of FAN1 to sites of damage is dependent upon its UBZ domain. In addition, knockdown of FAN1 by RNA interference leads to increased sensitivity to interstrand crosslinking agents and accumulation of abnormal chromosomes. FAN1 may be an important new player in the maintenance of genome stability.

Original languageEnglish (US)
Pages (from-to)3977-3983
Number of pages7
JournalCell Cycle
Volume9
Issue number19
DOIs
StatePublished - Oct 1 2010

Keywords

  • DNA damage
  • DNA repair
  • FAN1
  • Nuclease
  • UBZ
  • Ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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