TY - JOUR
T1 - A DNA recognition-mimicry switch governs induction in arbitrium phages
AU - Chmielowska, Cora
AU - Zamora-Caballero, Sara
AU - Mancheño-Bonillo, Javier
AU - Li, Yuyi
AU - Sin, Daniel
AU - Borenstein, Tom
AU - Bendori, Shira Omer
AU - Eldar, Avigdor
AU - Marina, Alberto
AU - Penadés, José R.
N1 - Publisher Copyright:
© 2026 The Author(s).
PY - 2026/2/11
Y1 - 2026/2/11
N2 - Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPbeta-like phages use arbitrium signaling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPbeta-like phage repressor, binds DNA via a mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of an antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognized by the repressor, thereby inactivating its function and inducing phage. This mechanism is conserved across SPbeta-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for efficient induction when arbitrium levels are high. Our results uncover the mechanism underlying a double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighboring prophages.
AB - Temperate phages integrate multiple information sources to regulate lysis-lysogeny transitions. SPbeta-like phages use arbitrium signaling and DNA damage to control repressor activity during lytic induction, but how the repressor functions and is inactivated by the SOS response remains unclear. Here, we show that SroF, the SPbeta-like phage repressor, binds DNA via a mechanism involving its integrase-like fold, enabling stable prophage repression. Upon DNA damage, the host SOS response triggers derepression of an antirepressor, Sar. Sar binds SroF by mimicking the DNA structure recognized by the repressor, thereby inactivating its function and inducing phage. This mechanism is conserved across SPbeta-like phages, which encode multiple, specific SroF-Sar pairs. Surprisingly, repressor inactivation alone is insufficient for efficient induction when arbitrium levels are high. Our results uncover the mechanism underlying a double layer of control that ensures phage induction occurs only under SOS conditions and in the absence of neighboring prophages.
KW - DNA damage
KW - SOS response
KW - activator
KW - lysis-lysogeny decision
KW - quorum sensing
KW - repressor
KW - temperate phages
UR - https://www.scopus.com/pages/publications/105029350005
U2 - 10.1016/j.chom.2026.01.012
DO - 10.1016/j.chom.2026.01.012
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C2 - 41619736
AN - SCOPUS:105029350005
SN - 1931-3128
VL - 34
SP - 291-303.e10
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 2
ER -