Controlling genome topology with sequences that trigger post-replication gap formation during replisome passage: the E. coli RRS elements

Phuong Pham; Elizabeth A Wood; Emma L Dunbar; Michael M Cox; Myron F Goodman

doi:10.1093/nar/gkae320

Controlling genome topology with sequences that trigger post-replication gap formation during replisome passage: the E. coli RRS elements

Nucleic Acids Res. 2024 Apr 27:gkae320. doi: 10.1093/nar/gkae320. Online ahead of print.

Authors

Phuong Pham¹, Elizabeth A Wood², Emma L Dunbar², Michael M Cox², Myron F Goodman¹

Affiliations

¹ Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA 90089-2910, USA.
² Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544, USA.

PMID: 38676944
DOI: 10.1093/nar/gkae320

Abstract

We report that the Escherichia coli chromosome includes novel GC-rich genomic structural elements that trigger formation of post-replication gaps upon replisome passage. The two nearly perfect 222 bp repeats, designated Replication Risk Sequences or RRS, are each 650 kb from the terminus sequence dif and flank the Ter macrodomain. RRS sequence and positioning is highly conserved in enterobacteria. At least one RRS appears to be essential unless a 200 kb region encompassing one of them is amplified. The RRS contain a G-quadruplex on the lagging strand which impedes DNA polymerase extension producing lagging strand ssDNA gaps, $ \le$2000 bp long, upon replisome passage. Deletion of both RRS elements has substantial effects on global genome structure and topology. We hypothesize that RRS elements serve as topological relief valves during chromosome replication and segregation. There have been no screens for genomic sequences that trigger transient gap formation. Functional analogs of RRS could be widespread, possibly including some enigmatic G-quadruplexes in eukaryotes.

Abstract

Grants and funding