Born to Slide: Mobile Origin Licensing Factors Confer Resistance to Transcription Conflicts
88 Pages Posted: 28 Jan 2021 Publication Status: Review CompleteMore...
Fundamental to our understanding of chromosome duplication is the idea that replication origins function both as sites where MCM helicases are loaded during the G1 phase and where synthesis begins in S phase. However, the temporal delay between these phases exposes the replisome assembly pathway to potential disruption prior to replication. Using multicolor, single-molecule imaging we systematically studied the consequences of encounters between actively transcribing RNA polymerases (RNAPs) and key replication initiation intermediates in the context of chromatin. We demonstrate that RNAP can push multiple licensed MCM helicases over long distances with individual nucleosomes overcome by ejection or displacement. Unexpectedly, we observe that MCM helicase loading intermediates can also be mobilized and repositioned by RNAP, providing a web of alternative origin specification pathways. Taken together, our observations reveal a surprising mobility in origin licensing factors that confers resistance to the complex challenges posed by diverse obstacles encountered on chromosomes.
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