Lachaud, C., Slean, M., Marchesi, F. , Lock, C., Odell, E., Castor, D., Toth, R. and Rouse, J. (2016) Karyomegalic interstitial nephritis and DNA damage-induced polyploidy in Fan1 nuclease-defective knock-in mice. Genes and Development, 30(6), pp. 639-644. (doi: 10.1101/gad.276287.115) (PMID:26980188) (PMCID:PMC4803050)
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Abstract
The Fan1 endonuclease is required for repair of DNA interstrand 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 from Fan1nd/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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Marchesi, Dr Francesco |
| Authors: | Lachaud, C., Slean, M., Marchesi, F., Lock, C., Odell, E., Castor, D., Toth, R., and Rouse, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | Genes and Development |
| Publisher: | Cold Spring Harbor Laboratory Press |
| ISSN: | 0890-9369 |
| ISSN (Online): | 1549-5477 |
| Published Online: | 15 March 2016 |
| Copyright Holders: | Copyright © 2016 2016 Lachaud et al. |
| First Published: | First published in Genes and Development 30:645-659 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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