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Control of the replication initiator DnaA by an anti‐cooperativity factor
Author(s) -
Merrikh Houra,
Grossman Alan D.
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2011.07821.x
Subject(s) - dnaa , biology , dna replication , pre replication complex , cooperativity , replisome , origin recognition complex , genetics , origin of replication , microbiology and biotechnology , replication factor c , processivity , seqa protein domain , dna , control of chromosome duplication , eukaryotic dna replication
Summary Proper coordination of DNA replication with cell growth and division is critical for production of viable progeny. In bacteria, coordination of DNA replication with cell growth is generally achieved by controlling activity of the replication initiator DnaA and its access to the chromosomal origin of replication, oriC . Here we describe a previously unknown mechanism for regulation of DnaA. YabA, a negative regulator of replication initiation in Bacillus subtilis , interacts with DnaA and DnaN, the sliding (processivity) clamp of DNA polymerase. We found that in vivo , YabA associated with the oriC region in a DnaA‐dependent manner and limited the amount of DnaA at oriC . In vitro , purified YabA altered binding of DnaA to DNA by inhibiting cooperativity. Although previously undescribed, proteins that directly inhibit cooperativity may be a common mechanism for regulating replication initiation. Conditions that cause release of DnaN from the replisome, or overproduction of DnaN, caused decreased association of YabA and increased association of DnaA with oriC . This effect of DnaN, either directly or indirectly, is likely responsible, in part, for enabling initiation of a new round of replication following completion of a previous round.