Which Of The cyclins Has Essential Function in S Phase of cell cycle?A.A type...B...B type..c.D type....D...Both B and D type
Answers
Cyclin-dependent kinase 2 (Cdk2) is essential for initiation of DNA synthesis in higher eukaryotes. Biochemical studies in Xenopus egg extracts and microinjection studies in human cells have suggested an additional function for Cdk2 in activation of Cdk1 and entry into mitosis. To further examine the role of Cdk2 in human cells, we generated stable clones with inducible expression of wild-type and dominant-negative forms of the enzyme (Cdk2-wt and Cdk2-dn, respectively). Both exogenous proteins associated efficiently with endogenous cyclins. Cdk2-wt had no apparent effect on the cell division cycle, whereas Cdk2-dn inhibited progression through several distinct stages. Cdk2-dn induction could arrest cells at the G1/S transition, as previously observed in transient expression studies. However, under normal culture conditions, Cdk2-dn induction primarily arrested cells with S and G2/M DNA contents. Several observations suggested that the latter cells were in G2 phase, prior to the onset of mitosis: these cells contained uncondensed chromosomes, low levels of cyclin B-associated kinase activity, and high levels of tyrosine-phosphorylated Cdk1. Furthermore, Cdk2-dn did not delay progression through mitosis upon release of cells from a nocodazole block. Although the G2 arrest imposed by Cdk2-dn was similar to that imposed by the DNA damage checkpoint, the former was distinguished by its resistance to caffeine. These findings provide evidence for essential functions of Cdk2 during S and G2 phases of the mammalian cell cycle.
A substantial body of evidence indicates that DNA synthesis in higher eukaryotes is initiated by activation of cyclin-dependent kinase 2 (Cdk2) (52, 66). Cdk2 associates with cyclin E and is activated shortly before S phase. The actual onset of S phase correlates closely with induction of cyclin A and its binding to Cdk2. Transient transfection of a catalytically inactive form of Cdk2 arrests cells in G1(74). This arrest was prevented by coexpression of wild-type (wt) Cdk2 (Cdk2-wt) but not other Cdks, suggesting that the mutant abrogates the function of endogenous Cdk2 in a dominant-negative (dn) manner. Similarly, addition of Cdk2 inhibitors or antibodies directed against Cdk2 to Xenopus egg extracts (19), microinjection of antibodies directed against Cdk2, cyclin A, or cyclin E in mammalian cells (54, 56, 73), or mutation of cyclin E in Drosophila (12, 13, 35) can block initiation of DNA synthesis. Candidate substrates of Cdk2 action at the G1-S transition include the retinoblastoma tumor suppressor protein (pRb), CDC6, and NPAT (32, 43, 57, 78, 81). Cdk2 is also implicated in duplication of centrosomes, another important event initiated at the G1/S boundary (26, 41, 46).
Evidence of a more limited scope suggests additional potential roles for Cdk2 in later cell cycle events. The catalytic activity of Cdk2, derived largely from its association with cyclin A, peaks in late S and G2 phases (55, 73). In some Drosophila tissues, mutation of cyclin A blocks mitotic entry in a cyclin B mutant background (36). In Xenopus egg extracts, Cdk2 complexes appear to be required for activation of Cdk1 (Cdc2), independently of Cdk2's role in DNA synthesis (23). In this setting, immunodepletion of Cdk2 or addition of p21WAF1/CIP1 blocks activation of Cdk1. The p21WAF1/CIP1 effect does not appear to result from direct binding to Cdk1, occurs even in the absence of nuclei, and can be rescued by addition of cyclin E-Cdk2 complexes. In HeLa cells, microinjection during S phase of antibodies directed against cyclin A can block cell division, without a gross effect on bromodeoxyuridine (BrdU) incorporation (56). This finding has been supported by two recent microinjection studies in human cells that have provided evidence that Cdk2 may be required to stabilize cyclin B (42) and/or to perform another step required to activate Cdk1 (21).
We have investigated the role of Cdk2 in human cell cycle progression by generating stable clones in which transcription of wt and dn forms of Cdk2 can be efficiently induced. This system permits flow cytometric and biochemical analysis of the effects of these proteins in cells that are proliferating exponentially or are synchronized at specific points in the cell cycle. Using these clones, we found that induction of Cdk2-wt had no apparent cell cycle effect, whereas induction of Cdk2-dn inhibited progression through several distinct phases of the cell cycle.
Answer:
Cyclin A or CDK2 has Essential Function in S Phase of cell cycle. Therefore, the correct answer would be A type.
Explanation:
The correct transition from G1 phase of the cell cycle to S section is critical for the control of eukaryotic cell proliferation, and its misregulation promotes oncogenesis. During G1 phase, growth-structured cyclin-structured kinase (CDK) activity promotes DNA replication and initiates G1-to-S phase transition. CDK activation initiates a positive feedback loop that in addition will increase CDK pastime, and this commits the cell to division via way of means of inducing genome-extensive transcriptional changes. G1–S transcripts encode proteins that alter downstream cell cycle events. Recent work is starting to expose the complicated molecular mechanisms that manage the temporal order of transcriptional activation and inactivation, decide awesome purposeful subgroups of genes and hyperlink cell cycle -structured transcription to DNA replication pressure in yeast and mammals.