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)

MRC PPU

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

242 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 (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

Access to Document

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

@article{6cb4ad42f23742f19a72573adfcdb625,

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.",

keywords = "FAN1, FANCD2, ICL, Fanconi anemia, KIN, karyomegaly",

author = "Christophe Lachaud and Meghan Slean and Francesco Marchesi and Claire Lock and Edward Odell and Dennis Castor and Rachel Toth and John Rouse",

year = "2016",

month = mar,

day = "15",

doi = "10.1101/gad.276287.115",

language = "English",

volume = "30",

pages = "639--644",

journal = "Genes and Development",

issn = "0890-9369",

publisher = "Cold Spring Harbor Laboratory Press",

number = "6",

}

TY - JOUR

T1 - Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in fan1 nuclease-defective knock-in mice

AU - Lachaud, Christophe

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

Y1 - 2016/3/15

N2 - 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.

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.

KW - FAN1

KW - FANCD2

KW - ICL

KW - Fanconi anemia

KW - KIN

KW - karyomegaly

UR - http://www.scopus.com/inward/record.url?scp=84961137920&partnerID=8YFLogxK

U2 - 10.1101/gad.276287.115

DO - 10.1101/gad.276287.115

M3 - Article

C2 - 26980188

AN - SCOPUS:84961137920

SN - 0890-9369

VL - 30

SP - 639

EP - 644

JO - Genes and Development

JF - Genes and Development

IS - 6

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Rouse, John

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Profiles

Rouse, John

Cite this