Snyder and Champness Molecular Genetics of Bacteria. Tina M. Henkin

Snyder and Champness Molecular Genetics of Bacteria - Tina M. Henkin


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by acidic phospholipids, and the other involves two sites found in the chromosome called DnaA-reactivating sequences (see Fujimitsu et al., Suggested Reading). The numerous inputs work together to limit the initiation of DNA replication to help keep the number of chromosomes consistent with the requirements for cell division.

      SeqA-MEDIATED HEMIMETHYLATION AND SEQUESTRATION

Schematic illustration of the replication creating hemimethylated DNA. (A) The A in the sequence GATC is methylated on both strands (Am and mA). (B) After replication, the A in GATC in the new strand is not immediately methylated by the Dam methylase. (C) Eventually, GATC sites in the new strand are methylated, converting the DNA back to the fully methylated state.

      SeqA activities outside of oriC

      In addition to the GATC/CTAG sequences associated with oriC and the dnaA promoter, SeqA also interacts with the GATC/CTAG sequences as the replication forks progress around the chromosome, effectively marking the location of the replisome (Figure 1.25). SeqA bound to transiently hemimethylated GATC/CTAG sites immediately behind the DNA replication forks may be capable of bringing together the nascent sister chromosomes, and it also appears to negatively regulate the decatenation activity of topoisomerase (see Joshi et al., Suggested Reading). Both of these processes may mediate a form of sister chromosome cohesion that in turn may help to regulate processing of the new DNAs by positioning them for DNA repair and recombination. Interestingly, SeqA is essential in mutants that lack the major pathways of DNA recombination involving RecA, supporting an additional role in protecting genome integrity. Additionally, chromosomes appear to be vulnerable to many types of mobile DNA elements during DNA replication, especially when replication forks stall (see Fricker and Peters, Suggested Reading). SeqA-facilitated processes may help to protect DNA replication forks from mobile elements as one of multiple mechanisms of protecting genome integrity.

      The nucleoid was described with respect to chromosome segregation above. Indeed, experiments in many of the model systems indicate that bacteria carefully coordinate the position of the chromosome in the cell. Through techniques in which individual positions in the chromosome can be localized in whole cells, it has been shown that genes are located in the chromosome in roughly the same order as one would presume by looking at the DNA sequence. A variety of techniques are providing insight into how the structure of the chromosome is maintained in the cell. The molecular mechanisms that maintain the chromosome structure remain a mystery, but specific systems are likely to exist to ensure that the chromosome is available for transcription, recombination, and other functions.


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