Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/117482
Title: | Differential requirements for Tousled-like kinases 1 and 2 in mammalian development |
Author: | Segura Bayona, Sandra Knobel, Philip A. González Burón, Helena Youssef, Sameh A. Peña Blanco, Aida Coyaud, Étienne López Rovira, Teresa Rein, Katrin Palenzuela, Lluís Colombelli, Julien Forrow, Stephen Raught, Brian Groth, Anja Bruin, Alain de Stracker, Travis H. |
Keywords: | Cromatina Proteïnes quinases Chromatin Protein kinases |
Issue Date: | 14-Jul-2017 |
Publisher: | Macmillan Publishers Limited |
Abstract: | The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1038/cdd.2017.108 |
It is part of: | Cell Death Differentiation, 2017, vol. 24, num. 11, p. 1872-1885 |
URI: | http://hdl.handle.net/2445/117482 |
DOI: | http://dx.doi.org/10.1038/cdd.2017.108 |
ISSN: | 1476-5403 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.