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The Role of MTBP as a Replication Origin Firing Factor.
Zaffar, Eman; Ferreira, Pedro; Sanchez-Pulido, Luis; Boos, Dominik.
Affiliation
  • Zaffar E; Molecular Genetics II, Centre for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.
  • Ferreira P; Molecular Genetics II, Centre for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.
  • Sanchez-Pulido L; Medical Research Council Human Genetics Unit, IGC, University of Edinburgh, Edinburgh EH9 3JR, UK.
  • Boos D; Molecular Genetics II, Centre for Medical Biotechnology, University of Duisburg-Essen, 45141 Essen, Germany.
Biology (Basel) ; 11(6)2022 May 27.
Article in En | MEDLINE | ID: mdl-35741348
The initiation step of replication at replication origins determines when and where in the genome replication machines, replisomes, are generated. Tight control of replication initiation helps facilitate the two main tasks of genome replication, to duplicate the genome accurately and exactly once each cell division cycle. The regulation of replication initiation must ensure that initiation occurs during the S phase specifically, that no origin fires more than once per cell cycle, that enough origins fire to avoid non-replicated gaps, and that the right origins fire at the right time but only in favorable circumstances. Despite its importance for genetic homeostasis only the main molecular processes of eukaryotic replication initiation and its cellular regulation are understood. The MTBP protein (Mdm2-binding protein) is so far the last core replication initiation factor identified in metazoan cells. MTBP is the orthologue of yeast Sld7. It is essential for origin firing, the maturation of pre-replicative complexes (pre-RCs) into replisomes, and is emerging as a regulation focus targeted by kinases and by regulated degradation. We present recent insight into the structure and cellular function of the MTBP protein in light of recent structural and biochemical studies revealing critical molecular details of the eukaryotic origin firing reaction. How the roles of MTBP in replication and other cellular processes are mutually connected and are related to MTBP's contribution to tumorigenesis remains largely unclear.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Biology (Basel) Year: 2022 Document type: Article Affiliation country: Alemania Country of publication: Suiza

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Biology (Basel) Year: 2022 Document type: Article Affiliation country: Alemania Country of publication: Suiza