title: Guard the guardian: A CRL4 ligase stands watch over histone production.
abstract: Histones are evolutionarily conserved proteins that together with DNA constitute eukaryotic chromatin in a defined stoichiometry. Core histones are dynamic scaffolding proteins that undergo a myriad of post-translational modifications, which selectively engage chromosome condensation, replication, transcription and DNA damage repair. Cullin4-RING ubiquitin E3 ligases are known to hold pivotal roles in a wide spectrum of chromatin biology ranging from chromatin remodeling and transcriptional repression, to sensing of cytotoxic DNA lesions. Our recent work uncovers an unexpected function of a CRL4 ligase upstream of these processes in promoting histone biogenesis. The CRL4WDR23ligase directly controls the activity of the stem-loop binding protein (SLBP), which orchestrates elemental steps of canonical histone transcript metabolism. We demonstrate that non-proteolytic ubiquitination of SLBP ensures sufficient histone reservoirs during DNA replication and is vital for genome integrity and cellular fitness.
authors.affiliation: a Institute of Biochemistry, ETH Zurich , Zürich , Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lampert
authors.affiliation: a Institute of Biochemistry, ETH Zurich , Zürich , Switzerland.|b nspm. ltd. , Meggen , Switzerland.
authors.forename: Mia M L
authors.initials: MM
authors.lastname: Brodersen
authors.affiliation: a Institute of Biochemistry, ETH Zurich , Zürich , Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
mesh_terms: D000818:Animals; D006657:Histones / Q000378:metabolism*; D006801:Humans; D055029:Inverted Repeat Sequences; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006657:Histones; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases
keywords: DNA replication; cullin-RING ligase (CRL); histone mRNA processing; stem–loop binding protein; ubiquitin