Talk:2010 Lecture 15

From CellBiology

Mammalian cells lack checkpoints for tetraploidy, aberrant centrosome number, and cytokinesis failure

http://www.biomedcentral.com/1471-2121/6/6

"Mammalian cells have been reported to have a p53-dependent tetraploidy checkpoint that blocks cell cycle progression in G1 in response to failure of cell division. .....We show that neither tetraploidy, aberrant centrosome number, cell size, nor failure of cytokinesis lead to G1 arrest, suggesting that there is no tetraploidy checkpoint. Rather, certain standard synchronization treatments cause damage that is the likely cause of G1 arrest. Since tetraploid cells can cycle when created with minimal manipulation, previous reports of a tetraploidy checkpoint can probably be explained by side effects of the drug treatments used to observe them."


Control and maintenance of mammalian cell size

http://www.biomedcentral.com/1471-2121/5/35

http://www.ncbi.nlm.nih.gov/pubmed/15456512

This view of the mammalian cell cycle, the continuum model, explains the mass growth pattern during the division cycle, size maintenance, size determination, and the kinetics of cell-size change following a shift-up from slow to rapid growth.

"Thus, there is no problem relating mass increase and the cell cycle. Cell mass growth and cell cycle passage cannot be dissociated because one (mass increase) is the determinant of the other (S-phase initiation). For this reason one needs neither checkpoints nor control elements outside of mass increase.

The time for mass to double in a particular situation determines the doubling time of a culture. This is because initiations of S phase occur every mass doubling time, and cell divisions similarly occur every mass doubling time. Thus total mass increases at the same rate as total cell number.


An essential role for Cdk1 in S phase control is revealed via chemical genetics in vertebrate cells

http://jcb.rupress.org/content/178/2/257.full?sid=e35576a0-efb7-4a92-be7d-706e7039d746

"In vertebrates Cdk1 is required to initiate mitosis; however, any functionality of this kinase during S phase remains unclear. To investigate this, we generated chicken DT40 mutants, in which an analog-sensitive mutant cdk1 as replaces the endogenous Cdk1, allowing us to specifically inactivate Cdk1 using bulky ATP analogs. In cells that also lack Cdk2, we find that Cdk1 activity is essential for DNA replication initiation and centrosome duplication. The presence of a single Cdk2 allele renders S phase progression independent of Cdk1, which suggests a complete overlap of these kinases in S phase control. Moreover, we find that Cdk1 inhibition did not induce re-licensing of replication origins in G2 phase. Conversely, inhibition during mitosis of Cdk1 causes rapid activation of endoreplication, depending on proteolysis of the licensing inhibitor Geminin. This study demonstrates essential functions of Cdk1 in the control of S phase, and exemplifies a chemical genetics approach to target cyclin-dependent kinases in vertebrate cells."


SABiosciences - Human Cell Cycle PCR Array The Human Cell Cycle RT² Profiler™ PCR Array profiles the expression of 84 genes key to cell cycle regulation. This array contains genes that both positively and negatively regulate the cell cycle, the transitions between the each of the phases, DNA replication, checkpoints and arrest. Using real-time PCR, you can easily and reliably analyze expression of a focused panel of genes related to the cell cycle with this array.

Checkpoints

cells are equipped with the checkpoints that are set at various stages of the cell cycle. When cells have DNA damages that have to be repaired, cells activate DNA damage checkpoint that arrests cell cycle. According to the cell cycle stages.

DNA damage checkpoints are classified into at least 3 checkpoints: G1/S (G1) checkpoint, intra-S phase checkpoint, and G2/M checkpoint. Upon perturbation of DNA replication by drugs that interfere with DNA synthesis, DNA lesions, or obstacles on DNA, cells activate DNA replication checkpoint that arrests cell cycle at G2/M transition until DNA replication is complete. There are more checkpoints such as Spindle checkpoint and Morphogenesis checkpoint. The spindle checkpoint arrests cell cycle at M phase until all chromosomes are aligned on spindle. This checkpoint is very important for equal distribution of chromosomes. Morphogenesis checkpoint detects abnormality in cytoskeleton and arrests cell cycle at G2/M transition.