Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in fan1 nuclease-defective knock-in mice

Christophe Lachaud, Meghan Slean, Francesco Marchesi, Claire Lock, Edward Odell, Dennis Castor, Rachel Toth, John Rouse (Lead / Corresponding author)

Research output: Contribution to journalArticle

13 Citations (Scopus)
113 Downloads (Pure)

Abstract

The Fan1 endonuclease is required for repair of DNAinterstrand cross-links (ICLs). Mutations in human Fan1 cause karyomegalic interstitial nephritis (KIN), but it is unclear whether defective ICL repair is responsible or whether Fan1 nuclease activity is relevant. We show that Fan1 nuclease- defective (Fan1nd/nd) mice develop a mild form of KIN. The karyomegalic nuclei from Fan1nd/nd kidneys are polyploid, and fibroblasts fromFan1nd/nd mice become polyploid upon ICL induction, suggesting that defective ICL repair causes karyomegaly. Thus, Fan1 nuclease activity promotes ICL repair in a manner that controls ploidy, a role that we show is not shared by the Fanconi anemia pathway or the Slx4–Slx1 nuclease also involved in ICL repair.

Original languageEnglish
Pages (from-to)639-644
Number of pages6
JournalGenes and Development
Volume30
Issue number6
DOIs
Publication statusPublished - 15 Mar 2016

Fingerprint

Interstitial Nephritis
Polyploidy
DNA Damage
Fanconi Anemia
Ploidies
Endonucleases
Fibroblasts
Kidney
Mutation

Keywords

  • FAN1
  • FANCD2
  • ICL
  • Fanconi anemia
  • KIN
  • karyomegaly

Cite this

Lachaud, Christophe ; Slean, Meghan ; Marchesi, Francesco ; Lock, Claire ; Odell, Edward ; Castor, Dennis ; Toth, Rachel ; Rouse, John. / Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in fan1 nuclease-defective knock-in mice. In: Genes and Development. 2016 ; Vol. 30, No. 6. pp. 639-644.
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Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in fan1 nuclease-defective knock-in mice. / Lachaud, Christophe; Slean, Meghan; Marchesi, Francesco; Lock, Claire; Odell, Edward; Castor, Dennis; Toth, Rachel; Rouse, John (Lead / Corresponding author).

In: Genes and Development, Vol. 30, No. 6, 15.03.2016, p. 639-644.

Research output: Contribution to journalArticle

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