AI Article Synopsis
- Replication initiation at specific DNA sites is crucial for accurate genetic duplication in eukaryotic cells.
- ORC proteins bind tightly to double-stranded DNA to help start this process, with a key role played by the origin sensor (EOS) in identifying the correct DNA regions.
- Research shows that ORC can also bind to single-stranded DNA and that this binding is enhanced by EOS, which may influence ORC activity and function across different eukaryotic organisms.
Article Abstract
Replication initiation at specific genomic loci dictates precise duplication and inheritance of genetic information. In eukaryotic cells, ATP-bound origin recognition complexes (ORCs) stably bind to double-stranded (ds) DNA origins to recruit the replicative helicase onto the origin DNA. To achieve these processes, an essential region of the origin DNA must be recognized by the eukaryotic origin sensor (EOS) basic patch within the disordered domain of the largest ORC subunit, Orc1. Although ORC also binds single-stranded (ss) DNA in an EOS-independent manner, it is unknown whether EOS regulates ORC on ssDNA. We found that, in budding yeast, ORC multimerizes on ssDNA in vitro independently of adenine nucleotides. We also found that the ORC multimers form in an EOS-dependent manner and stimulate the ORC ATPase activity. An analysis of genomics data supported the idea that ORC-ssDNA binding occurs in vivo at specific genomic loci outside of replication origins. These results suggest that EOS function is differentiated by ORC-bound ssDNA, which promotes ORC self-assembly and ATP hydrolysis. These mechanisms could modulate ORC activity at specific genomic loci and could be conserved among eukaryotes.
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| http://dx.doi.org/10.1111/gtc.12710 | DOI Listing |
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