1. Chapter 11 Replication Is Connected to the Cell Cycle

2. 11.1 Introduction
Figure 11.01: A growing cell alternates between cell division of a mother cell into two daughter cells and growth back to the original size.
Figure 11.02: Replication initiates at the bacterial origin when a cell passes a critical threshold of size.

3. 11.2 Bacterial Replication Is Connected to the Cell Cycle
The doubling time of E. coli can vary over a 10x range, depending on growth conditions.
It requires 40 minutes to replicate the bacterial chromosome (at normal temperature).
Completion of a replication cycle triggers a bacterial division 20 minutes later.

4. 11.2 Replication Is Connected to the Cell Cycle
If the doubling time is ~60 minutes, a replication cycle is initiated before the division resulting from the previous replication cycle.
Fast rates of growth therefore produce multiforked chromosomes.
Figure 11.03: The fixed interval of 60 minutes between initiation of replication and cell division produces multiforked chromosomes in rapidly growing cells.

5. 11.3 The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome
anucleate cell – Bacteria that lack a nucleoid but are of similar shape to wild-type bacteria.
Bacterial chromosomes are specifically arranged and positioned inside cells.
Septum formation is initiated mid-cell, 50% of the distance from the septum to each end of the bacterium.

6. 11.3 The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome
Figure 11.04: Attachment of bacterial DNA to the membrane could provide a mechanism for segregation.

7. 11.3 The Septum Divides a Bacterium into Progeny That Each Contain a Chromosome
The septum consists of the same peptidoglycans that comprise the bacterial envelope.
The rod shape of E. coli is dependent on MreB, PBP2, and RodA.
FtsZ is necessary to recruit the enzymes needed to form the septum.

8. 11.4 Mutations in Division or Segregation Affect Cell Shape
fts mutants form long filaments because the septum that divides the daughter bacteria fails to form.
Minicells form in mutants that produce too many septa.
They are small and lack DNA.
Anucleate cells of normal size are generated by partition mutants in which the duplicate chromosomes fail to separate.

9. 11.5 FtsZ Is Necessary for Septum Formation
The product of ftsZ is required for septum formation at pre-existing sites.
FtsZ is a GTPase that forms a ring (the Z-ring or septal ring) on the inside of the bacterial envelope.
It is connected to other cytoskeletal components.

10. 11.6 min and noc/slm Genes Regulate the Location of the Septum
The location of the septum is controlled by minC, -D, and –E and by noc/slm.
The number and location of septa is determined by the ratio of MinE/MinC,D.
Dynamic movement of the Min proteins in the cell sets up a pattern in which inhibition of Z-ring assembly is highest at the poles and lowest at midcell.
Slm/Noc proteins prevent septation from occurring in the space occupied by the bacterial chromosome.

11. 11.6 min and noc/slm Genes Regulate the Location of the Septum
Figure 11.08: MinC/D is a division inhibitor whose action is confined to the poles by MinE.

12. 11.7 Chromosomal Segregation May Require Site-Specific Recombination
The Xer site-specific recombination system acts on a target sequence near the chromosome terminus.
It recreates monomers if a generalized recombination event has converted the bacterial chromosome to a dimer.
Figure 11.09: Intermolecular recombination merges monomers into dimers, and intramolecular recombination releases individual units from oligormers.

13. 11.7 Chromosomal Segregation May Require Site-Specific Recombination
Figure 11.10: A circular chromosome replicates to produce two monomeric daughters that segregate to daughter cells.
Figure 11.11: A recombination event creates two linked chromosomes. Xer creates a Holliday junction at the dif site, but can resolve it only in the presence of FtsK.

14. 11.8 Partitioning Separates the Chromosomes
Replicon origins are attached to the inner bacterial membrane.
Chromosomes make abrupt movements from the midcenter to the one-quarter and three-quarter positions.
Figure 11.12: The DNA of a single parental nucleoid becomes decondensed during replication. MukB is an essential component of the apparatus that recondenses the daughter nucleoids.

15. 11.9 The Eukaryotic Growth Factor Signal Transduction Pathway
signal transduction pathway - The process by which a stimulus or cellular state is sensed by and transmitted to pathways within the cell.
oncogene - A gene that when mutated may cause cancer.
The function of a growth factor is to cause dimerization of its receptor and subsequent phosphorylation of the cytoplasmic domain of the receptor.

16. 11.9 The Eukaryotic Growth Factor Signal Transduction Pathway
The function of the growth factor receptor is to recruit the exchange factor SOS to the membrane to activate RAS.
The function of activated RAS is to recruit RAF to the membrane to become activated.
The function of RAF is to initiate a phosphorylation cascade leading to the phosphorylation of a set of transcription factors that can enter the nucleus and begin S phase.

17. 11.9 The Eukaryotic Growth Factor Signal Transduction Pathway
Figure 11.13: Growth Factors and Growth Factor Receptors

18. 11.10 Checkpoint Control for Entry into S Phase: p53, A Guardian of the Checkpoint
The tumor suppressor proteins p53 and Rb act as guardians of the cell.
A set of serine/threonine protein kinases called cyclin-dependent kinases (CDKs) control cell cycle progression.
Cyclin proteins are required to activate CDK proteins.

19. 11.10 Checkpoint Control for Entry into S Phase: p53, A Guardian of the Checkpoint
A set of inhibitor proteins negatively regulate the cyclin/CDKs.
A set of activator proteins, CAKs, positively regulate the cyclin/CDKs.
Figure 11.15: Formation of an active CDK requires binding to a cyclin. The process is regulated by positive and negative factors.

20. Figure 11.16: DNA damage pathway.
Checkpoint Control for Entry into S Phase: p53, A Guardian of the Checkpoint
Figure 11.16: DNA damage pathway.

21. 11.11 Checkpoint Control for Entry into S Phase: Rb, a Guardian of the Checkpoint
restriction point - The point during G1 at which a cell becomes committed to division.
Rb is the major guardian of the cell cycle, integrating information about DNA damage and cell growth.

22. 11.11 Checkpoint Control for Entry into S Phase: Rb, a Guardian of the Checkpoint
Rb binds to an essential transcription factor, E2F, to prevent it from turning on the genes required for cell cycle progression.
When Rb is phosphorylated by a Cyclin/CDK complex, it releases E2F to permit cell progression.
Figure 11.17: Growth factors are required to start the cell cycle and continue into S phase.