scholarly journals Cytolethal Distending Toxin Type I and Type IV Genes Are Framed with Lambdoid Prophage Genes in Extraintestinal Pathogenic Escherichia coli

2008 ◽  
Vol 77 (1) ◽  
pp. 492-500 ◽  
Author(s):  
István Tóth ◽  
Jean-Philippe Nougayrède ◽  
Ulrich Dobrindt ◽  
Terence Neil Ledger ◽  
Michèle Boury ◽  
...  

ABSTRACT Five types of cytolethal distending toxin (CDT-I to CDT-V) have been identified in Escherichia coli. In the present study we cloned and sequenced the cdt-IV operon and flanking region from a porcine extraintestinal pathogenic E. coli (ExPEC) strain belonging to serogroup O75. We confirmed that similar to other CDTs, CDT-IV induced phosphorylation of host histone H2AX, a sensitive marker of DNA double-strand breaks, and blocked the HeLa cell cycle at the G2-M transition. The cdt-IV genes were framed by lambdoid prophage genes. We cloned and sequenced the cdt-I operon and flanking regions from a human ExPEC O18:K1:H7 strain and observed that cdt-I genes were also flanked by lambdoid prophage genes. PCR studies indicated that a gene coding for a putative protease was always associated with the cdtC-IV gene but was not associated with cdtC genes in strains producing CDT-I, CDT-III, and CDT-V. Our results suggest that the cdt-I and cdt-IV genes might have been acquired from a common ancestor by phage transduction and evolved in their bacterial hosts. The lysogenic bacteriophages have the potential to carry nonessential “cargo” genes or “morons” and therefore play a crucial role in the generation of genetic diversity within ExPEC.

Biochimie ◽  
2018 ◽  
Vol 148 ◽  
pp. 116-126 ◽  
Author(s):  
Isidoro Feliciello ◽  
Davor Zahradka ◽  
Ksenija Zahradka ◽  
Siniša Ivanković ◽  
Nikolina Puc ◽  
...  

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Israel Salguero ◽  
Rimma Belotserkovskaya ◽  
Julia Coates ◽  
Matylda Sczaniecka-Clift ◽  
Mukerrem Demir ◽  
...  

AbstractHistone H2AX and MDC1 are key DNA repair and DNA-damage signalling proteins. When DNA double-strand breaks (DSBs) occur, H2AX is phosphorylated and then recruits MDC1, which in turn serves as a docking platform to promote the localization of other factors, including 53BP1, to DSB sites. Here, by using CRISPR-Cas9 engineered human cell lines, we identify a hitherto unknown, H2AX-independent, function of MDC1 mediated by its PST-repeat region. We show that the PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin. We find that this region is largely functionally dispensable when the canonical γH2AX-MDC1 pathway is operative but becomes critical for 53BP1 recruitment to DNA-damage sites and cell survival following DSB induction when H2AX is not available. Consequently, our results suggest a role for MDC1 in activating the DDR in areas of the genome lacking or depleted of H2AX.


PLoS Genetics ◽  
2017 ◽  
Vol 13 (10) ◽  
pp. e1006895 ◽  
Author(s):  
Anurag Kumar Sinha ◽  
Adeline Durand ◽  
Jean-Michel Desfontaines ◽  
Ielyzaveta Iurchenko ◽  
Hélène Auger ◽  
...  

2005 ◽  
Vol 164 (4) ◽  
pp. 514-517 ◽  
Author(s):  
Francesca Antonelli ◽  
Mauro Belli ◽  
Giacomo Cuttone ◽  
Valentina Dini ◽  
Giuseppe Esposito ◽  
...  

2008 ◽  
Vol 29 (4) ◽  
pp. 1050-1058 ◽  
Author(s):  
Omar Zgheib ◽  
Kristopher Pataky ◽  
Juergen Brugger ◽  
Thanos D. Halazonetis

ABSTRACT 53BP1, the vertebrate ortholog of the budding yeast Rad9 and fission yeast Crb2/Rhp9 checkpoint proteins, is recruited rapidly to sites of DNA double-strand breaks (DSBs). A tandem tudor domain in human 53BP1 that recognizes methylated residues in the histone core is necessary, but not sufficient, for efficient recruitment. By analysis of deletion mutants, we identify here additional elements in 53BP1 that facilitate recognition of DNA DSBs. The first element corresponds to an independently folding oligomerization domain. Replacement of this domain with heterologous tetramerization domains preserves the ability of 53BP1 to recognize DNA DSBs. A second element is only about 15 amino acids long and appears to be a C-terminal extension of the tudor domain, rather than an independently functioning domain. Recruitment of 53BP1 to sites of DNA DSBs is facilitated by histone H2AX phosphorylation and ubiquitination. However, none of the 53BP1 domains/elements important for recruitment are known to bind phosphopeptides or ubiquitin, suggesting that histone phosphorylation and ubiquitination regulate 53BP1 recruitment to sites of DNA DSBs indirectly.


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