The decatenation and segregation of the newly replicated chromosomes to each of the daughter cells are highly accurate. Even the highly asymmetric segregation of sporulating B. subtilis chromosomes leaves less than 0.02% of anucleate cells (46). While the chromosome is replicated, cells elongate and a septum forms at the cell center. There, translocases, such as FtsK in E. coli and SpoIIIE in B. subtilis , direc- tionally pump DNA into the daughter cells by recognizing motifs that point to the dif site. In E. coli , these motifs are called KOPS (FtsK orienting polar sequences) and their density is higher in the leading strand and increases toward the replication terminus, thereby in- dicating the direction of DNA translocation (7, 62). KOPS polarity constrains the chromo- some dynamics near the terminus of replica- tion because inversions lead to inversely polar- ized KOPS and therefore to a disruption of the 220 Rocha Annu. Rev. Genet. 2008.42:211-233. Downloaded from arjournals.annualreviews.org by BIUS Jussieu - Multi-Site on 11/05/08. For personal use only.
5' 3' 3' 5' 3' 5' a b Okazaki fragments (L O ) Transcript (L t ) Collision fork/RNAP Truncated mRNA (T): T lag = 100% T lead = (1-V RNAP /V fork, lead ) × 100 = 91% RNAP exclusion time (t x ): t x, lag = L O /V fork, lag +L t /V fork, lag + L t /V RNAP = 52.7 s t x, lead = L t /V RNAP - L t /V fork, lead = 36.5 s 100 × t x, lag /t d = 4.4% 100 × t x, lead /t d = 3.0% Primase Helicase Terminator Promoter DNA polymerase Effect on total expression (%): Figure 4 Outcome of collisions between the fork and the RNA polymerase (RNAP) when genes are in the lagging ( red ) and leading ( aqua ) strands and collisions do not lead to replication arrests (in which case the impact of collisions is more important). Truncated mRNA refers to the fraction of aborted transcriptions while the fork passes in the transcribed region and assumes that all co-oriented collisions lead to transcription abortion (therefore the estimated difference is conservative). RNAP exclusion is the time when the region is unavailable for transcription. The effect on total expression of genes is the latter value time divided by the optimal doubling time (t d ). Computations and results (using parameters in B. subtilis ) are detailed in supplementary material . (Follow the Supplemental Material link from the Annual Reviews home page at ). The variables V x refer to the rate of RNAP or the replication fork (nt/s). decatenation process. As a result, some inver- sions in these regions are lethal, whereas dele- tions are viable, providing a striking example where genome organization prevails over gene content (88). GENE STRAND BIAS AND THE ANTAGONISM BETWEEN REPLICATION AND GENE EXPRESSION The replication fork synthesizes one DNA strand continuously, the leading strand, and the other semidiscontinuously, the lagging strand ( Figure 4 ). The different replication mode of the two strands leads to different mutational patterns. As a result, the leading strand tends to be richer in G and the lagging strand richer in C in the vast majority of bacterial genomes (66), albeit from different mutational causes (89). This compositional bias allows the iden-
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