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\begin{document}

\title{The Insertion Sequence Excision Enhancer (IEE): a PrimPol-based system
for Immobilizing Transposon-Transmitted Antibiotic Resistance Genes?}



\author[1]{Michael Chandler}%
\author[1]{Karen Ross}%
\author[2]{Alessandro de Mello Varani}%
\affil[1]{Georgetown University Medical Center}%
\affil[2]{Universidade Estadual Paulista Julio de Mesquita Filho - Campus de Jaboticabal}%


\vspace{-1em}



  
  \date{May 25, 2024}


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\begin{abstract}
Evolutionary studies often identify genes that are shared between
different organisms and the phrase Lateral or Horizontal Gene Transfer
is often used in this context. However, they rarely provide any
mechanistic information concerning how these gene transfers might have
occurred. With the astonishing increase in the number of sequences in
the public databases over the past two or three decades, identical
antibiotic resistance genes have been identified in many different
sequence contexts. One explanation for this would be that genes are
initially transmitted by transposons which have subsequently decayed and
can no longer be detected. Here, we provide an overview of a protein,
IEE (Insertion Sequence Excision Enhancer) observed to facilitate high
frequency excision of IS \emph{629} from clinically important
\emph{Escherichia coli} O157:H7 and subsequently shown to affect a large
class of bacterial insertion sequences which all transpose by using the
copy-out-paste-in transposition mechanism. Excision depends on both IEE
and transposase indicating association with the transposition process
itself. We review genetic and biochemical data and propose that IEE
immobilizes genes carried by compound transposons by removing the
flanking IS copies. The biochemical activities of IEE as a primase with
the capacity to recognize DNA microhomologies and the observation that
its effect appears restricted to IS families which use copy-out-paste-in
transposition, suggests IS deletion occurs by abortive transposition
involving strand switching during the copy-out step. This reinforces the
proposal made for understanding loss of IS \emph{Apl1} flanking
\emph{mcr}-1 in the compound transposon Tn \emph{6330} which we
illustrate with a detailed model.%
\end{abstract}%



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\verb`The Insertion Sequence Excision Enhancer_for Mol Mic.docx`  available at \url{https://authorea.com/users/627348/articles/648330-the-insertion-sequence-excision-enhancer-iee-a-primpol-based-system-for-immobilizing-transposon-transmitted-antibiotic-resistance-genes}

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