UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival.

Autor:	Lee L; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Perez Oliva AB; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain.; Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain., Martinez-Balsalobre E; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain., Churikov D; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Peter J; MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK., Rahmouni D; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Audoly G; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Azzoni V; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Audebert S; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Camoin L; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Mulero V; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain.; Departamento de Biología Celular e Histología, Facultad de Biología, Universidad de Murcia, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain., Cayuela ML; Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Centro de Investigación Biomédica en Red de Enfermedades Raras, Murcia, Spain., Kulathu Y; MRC Protein Phosphorylation & Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, UK., Geli V; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France., Lachaud C; Aix-Marseille Univ, INSERM, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Sep 24; Vol. 7 (39), pp. eabc7371. Date of Electronic Publication: 2021 Sep 24.
DOI:	10.1126/sciadv.abc7371
Abstrakt:	Ubiquitin-fold modifier 1 (UFM1) is involved in neural and erythroid development, yet its biological roles in these processes are unknown. Here, we generated zebrafish models deficient in Ufm1 and Ufl1 that exhibited telomere shortening associated with developmental delay, impaired hematopoiesis and premature aging. We further report that HeLa cells lacking UFL1 have instability of telomeres replicated by leading-strand synthesis. We uncover that MRE11 UFMylation is necessary for the recruitment of the phosphatase PP1-α leading to dephosphorylation of NBS1. In the absence of UFMylation, NBS1 remains phosphorylated, thereby reducing MRN recruitment to telomeres. The absence of MRN at telomeres favors the formation of the TRF2-Apollo/SNM1 complex consistent with the loss of leading telomeres. These results suggest that MRE11-UFMylation may serve as module to recruit PP1-α. Last, zebrafish expressing Mre11 that cannot be UFMylated phenocopy Ufm1 -deficient zebrafish, demonstrating that UFMylation of MRE11 is a previously undescribed evolutionarily conserved mechanisms regulating telomere length.
Databáze:	MEDLINE
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