98%
921
2 minutes
20
The rnhAB mutants of Escherichia coli lacking both RNase H enzymes are unexpectedly UV-sensitive, being unable to restore normal levels of post-UV replication. Examining patterns of chromosomal replication in the rnhAB mutants after UV could identify the problem sites. We show that normal rnhA (B) mutant replication initiates at three distinct oriK areas in the origin macrodomain, none of them coinciding with oriC proper, the dominant origin being some 400 kb away. Interestingly, initiation after UV switches to the DnaA-dependent oriK closest to oriC and continues from there until the growth replication pattern is restored, like in the rnhA single mutants. However, in the rnhAB double mutant, post-UV forks initiated at the new origin have difficulty reaching the terminus, with the major stalling sites at the rrn operons. In the rnhAB recBC mutants, additionally deficient in linear DNA degradation/repair, post-UV replication forks cannot traverse the origin-distal ribosomal RNA operons, rrnG and rrnH, showing that restoration of disintegrated replication forks is essential for replication in the rnhAB mutant. In contrast, the rnhAB rpoB* mutant, in which transcription complexes are unstable, is UV-resistant and resumes normal replication even faster than WT cells, indicating that the rnhAB mutants suffer from UV-induced replication-transcription conflicts.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000880 | PMC |
http://dx.doi.org/10.1093/nar/gkaf282 | DOI Listing |
Nucleic Acids Res
April 2025
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
The rnhAB mutants of Escherichia coli lacking both RNase H enzymes are unexpectedly UV-sensitive, being unable to restore normal levels of post-UV replication. Examining patterns of chromosomal replication in the rnhAB mutants after UV could identify the problem sites. We show that normal rnhA (B) mutant replication initiates at three distinct oriK areas in the origin macrodomain, none of them coinciding with oriC proper, the dominant origin being some 400 kb away.
View Article and Find Full Text PDFJ Bacteriol
October 2023
Department of Microbiology, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
Ribonucleotides frequently contaminate DNA and, if not removed, cause genomic instability. Consequently, all organisms are equipped with RNase H enzymes to remove RNA-DNA hybrids (RDHs). lacking RNase HI () and RNase HII () enzymes, the ∆ ∆ double mutant, accumulates RDHs in its DNA.
View Article and Find Full Text PDFNucleic Acids Res
April 2021
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Ultraviolet (UV) induces pyrimidine dimers (PDs) in DNA and replication-dependent fragmentation in chromosomes. The rnhAB mutants in Escherichia coli, accumulating R-loops and single DNA-rNs, are generally resistant to DNA damage, but are surprisingly UV-sensitive, even though they remove PDs normally, suggesting irreparable chromosome lesions. We show here that the RNase H defect does not cause additional chromosome fragmentation after UV, but inhibits DNA synthesis after replication restart.
View Article and Find Full Text PDFJ Mol Biol
September 2017
Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address:
The rnhAB mutant Escherichia coli, deficient in two RNase H enzymes that remove both R-loops and incorporated ribonucleotides (rNs) from DNA, grow slowly, suggesting accumulation of rN-containing DNA lesions (R-lesions). We report that the rnhAB mutants have reduced viability, form filaments with abnormal nucleoids, induce SOS, and fragment their chromosome, revealing replication and/or segregation stress. R-loops are known to interfere with replication forks, and sensitivity of the double rnhAB mutants to translation inhibition points to R-loops as precursors for R-lesions.
View Article and Find Full Text PDF