Targeting and association of proteins with functional domains in the nucleus: the insoluble solution.
The mammalian nucleus is highly organized into distinct functional domains separating different biochemical processes such as transcription, RNA processing, DNA synthesis, and ribosome assembly. A number of proteins known to participate in these processes were found to be specifically localized at their corresponding functional domains. A distinct targeting sequence, necessary and sufficient for the localization to DNA replication foci, was identified in the N-terminal, regulatory domain of DNA methyltransferase and DNA ligase I and might play a role in the coordination of DNA replication and DNA methylation. The fact that the targeting sequence is absent in lower eukaryotic and prokaryotic DNA ligase I homologs suggests that "targeting" is a rather recent development in evolution. Finally, targeting sequences have also been identified in some splicing factors and in viral proteins, which are responsible for their localization to the speckled compartment and to the nucleolus, respectively. These higher levels of organization are likely to contribute to the regulation and coordination of the complex and interdependent biochemical processes in the mammalian nucleus.
Leonhardt
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Humboldt Universität Berlin, Franz-Volhard-Klinik am Max-Delbrück-Centrum für Molekulare Medizin, Department of Nephrology, Hypertension, and Genetics, Germany.
Cardoso
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MC
D000818:Animals; D001665:Binding Sites; D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry / Q000378:metabolism; D015254:DNA Modification Methylases / Q000737:chemistry / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
C000607892:LIG1 protein, human; D009687:Nuclear Proteins; D012313:RNA; D015254:DNA Modification Methylases; D011088:DNA Ligases; D000072481:DNA Ligase ATP