The HU protein is a small, basic, heat-stable DNA-binding protein that is 
well-conserved in prokaryotes and is associated with the bacterial nucleoid. In 
enterobacteria, including Escherichia coli, HU is a heterotypic dimer, 
HUalphabeta, composed of two closely related sub-units encoded by the hupA and 
hupB genes, respectively. HU was shown to participate in vitro in the initiation 
of DNA replication as an accessory factor to assist the action of DnaA protein 
in the unwinding of oriC DNA. To further elucidate the role of HU in the 
regulation of the DNA replication initiation process, we tested the synchrony 
phenotype in the absence of either one or both HU sub-units. The hupAB mutant 
exhibits an asynchronous initiation, the hupA mutant shows a similar reduced 
synchrony, whereas the hupB mutant shows a normal phenotype. Using a 
thermosensitive dnaA46 strain (dnaA46ts), an initiation mutant, we reveal a 
special role of HUbeta. The presence of a plasmid overproducing HUbeta in a 
dnaA46ts lacking HU (hupAB background) compensates for the thermosensitivity of 
this initiation mutant. Moreover, the overproduction of HUbeta confers to 
dnaA46ts a pattern of asynchrony similar to that of a dnaAcos, the intragenic 
suppressor of dnaA46ts. We show that the relative ratio of HUalpha versus HUbeta 
is greatly perturbed in dnaA46ts which accumulates little, if any, HUbeta. 
Therefore, the suppression of thermosensitivity in dnaA46hupAB by HUbeta may be 
caused by an unexpected absence of HUbeta in the dnaA46ts mutant. Visibly the HU 
composition is sensitive to the different states of DnaA, and may play a role 
during the regulation of the initiation process of the DNA replication by 
affecting subsequent events along the cell cycle.