Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair.
The nucleolus represents a highly multifunctional intranuclear organelle in which, in addition to the canonical ribosome assembly, numerous processes such as transcription, DNA repair and replication, the cell cycle, and apoptosis are coordinated. The nucleolus is further a key hub in the sensing of cellular stress and undergoes major structural and compositional changes in response to cellular perturbations. Numerous nucleolar proteins have been identified that, upon sensing nucleolar stress, deploy additional, non-ribosomal roles in the regulation of varied cell processes including cell cycle arrest, arrest of DNA replication, induction of DNA repair, and apoptosis, among others. The highly abundant proteins nucleophosmin (NPM1) and nucleolin (NCL) are two such factors that transit to the nucleoplasm in response to stress, and participate directly in the repair of numerous different DNA damages. This review discusses the contributions made by NCL and (or) NPM1 to the different DNA repair pathways employed by mammalian cells to repair DNA insults, and examines the implications of such activities for the regulation, pathogenesis, and therapeutic targeting of NPM1 and NCL.
a Laboratory of RNP Biochemistry, Institut de recherches cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada.|b Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC H3A 2A3, Canada.
Daniel D
DD
Scott
a Laboratory of RNP Biochemistry, Institut de recherches cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada.|b Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, QC H3A 2A3, Canada.|c Département de biochimie et médecine moléculaire, Faculté de Médecine, Université de Montréal, QC H3T 1J4, Canada.
Marlene
M
Oeffinger
D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000097796:Nucleolin
D009687:Nuclear Proteins; D000090243:Nucleophosmin; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C000716967:NPM1 protein, human
DNA damage; DNA repair; dommage à l’ADN; nucleolin; nucleolus; nucleophosmin; nucléole; nucléoline; nucléophosmine; réparation d’ADN