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

doi:10.1101/gad.276287.115

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)

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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 (Fan1^nd/nd) mice develop a mild form of KIN. The karyomegalic nuclei from Fan1^nd/nd kidneys are polyploid, and fibroblasts fromFan1^nd/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 language	English
Pages (from-to)	639-644
Number of pages	6
Journal	Genes and Development
Volume	30
Issue number	6
DOIs	https://doi.org/10.1101/gad.276287.115
Publication status	Published - 15 Mar 2016

Keywords

FAN1
FANCD2
ICL
Fanconi anemia
KIN
karyomegaly

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.276287.115Licence: CC BY

Final Published Version
© 2016 Lachaud et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Final published version, 559 KBLicence: CC BY
Final Published Version - Supplementary Material
© 2016 Lachaud et al. This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
Final published version, 1.97 MBLicence: CC BY

Cite this

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title = "Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in fan1 nuclease-defective knock-in mice",

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.",

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AU - Slean, Meghan

AU - Marchesi, Francesco

AU - Lock, Claire

AU - Odell, Edward

AU - Castor, Dennis

AU - Toth, Rachel

AU - Rouse, John

PY - 2016/3/15

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AB - 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.

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

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Rouse, John

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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Rouse, John

Cite this