Common structural features of replication origins in all life forms.
Origins of replication (ORIs) among prokaryotes, viruses, and multicellular organisms appear to possess simple tri-, tetra-, or higher dispersed repetitions of nucleotides, AT tracts, inverted repeats, one to four binding sites of an initiator protein, intrinsically curved DNA, DNase I-hypersensitive sites, a distinct pattern of DNA methylation, and binding sites for transcription factors. Eukaryotic ORIs are sequestered on the nuclear matrix; this attachment is supposed to facilitate execution of their activation/deactivation programs during development. Furthermore, ORIs fall into various classes with respect to their sequence complexity: those enriched in AT tracts, those with GA- and CT-rich tracts, a smaller class of GC-rich ORIs, and a major class composed of mixed motifs yet containing distinct AT and polypurine or GC stretches. Multimers of an initiator protein in prokaryotes and viruses that might have evolved into a multiprotein replication initiation complex in multicellular organisms bind to the core ORI, causing a structural distortion to the DNA which is transferred to the AT tract flanking the initiator protein site; single-stranded DNA-binding proteins then interact with the melted AT tract as well as with the DNA polymerase alpha-primase complex in animal viruses and mammalian cells, causing initiation in DNA replication. ORIs in mammalian cells seem to colocalize with matrix-attached regions and are proposed to become DNase I-hypersensitive during their activation.
Boulikas
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Institute of Molecular Medical Sciences, Palo Alto, California 94306, USA.
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D018741:Replication Origin / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology
D014157:Transcription Factors; D004247:DNA