During cell cycle, entry in the S-phase is tightly regulated. This is possible because: A. APC/C promotes ubiquitination of S-phase cyclins and mitotic cyclins, marking them for proteolyses at the mitotic exit. B. Cyclin B1 helps in the activation of S-phase CDKs only in late G1. C. As mitotic CDK activity declines in late mitosis, cdc14 phosphatase activates APC/C by dephosphorylating Cdh1, thus promoting formation of APC/CCdh1 D. Securin keeps S-phase cyclins in inactive state till late G1. Which one of the options represents all correct statements?
A and C
Cell Cycle S-phase Regulation Explained
The cell cycle is a fundamental process that ensures accurate duplication of a cell's genetic material and its division into two daughter cells. Entry into the S-phase, where DNA replication occurs, is a critical transition that is tightly controlled to prevent errors in DNA replication and maintain genomic stability.
This tight regulation is achieved through the coordinated activity of various proteins, including cyclins, CDKs (Cyclin-Dependent Kinases), and protein degradation machinery like the APC/C (Anaphase Promoting Complex/Cyclosome).
Statement Analysis: Cell Cycle Entry
Let's analyze each statement provided regarding the regulation of S-phase entry:
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A. APC/C promotes ubiquitination of S-phase cyclins and mitotic cyclins, marking them for proteolyses at the mitotic exit.
The APC/C is a ubiquitin ligase that is active from late mitosis throughout G1. Its activity is crucial for exiting mitosis and preventing premature entry into S-phase. APC/C, primarily associated with Cdh1 (APC/CCdh1) during G1, targets various proteins for degradation by the proteasome. This includes mitotic cyclins (like Cyclin B) and S-phase cyclins (like Cyclin A and Cyclin E). The degradation of these cyclins keeps CDK activity low during G1, creating a favorable environment for replication origin licensing but preventing the activation of S-phase CDKs until the cell is ready to commit to DNA replication. Thus, this statement is correct.
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B. Cyclin B1 helps in the activation of S-phase CDKs only in late G1.
Cyclin B1 is a mitotic cyclin that primarily associates with CDK1 (also known as Cdc2) to form the complex known as MPF (Maturation Promoting Factor), which drives the cell into mitosis. S-phase CDKs are typically formed by Cyclin E and Cyclin A associating with CDK2. Cyclin B1 levels rise in G2 and M phase and are low in G1. Therefore, Cyclin B1 is involved in regulating entry into and progression through mitosis, not in activating S-phase CDKs or regulating late G1 events leading to S-phase entry. This statement is incorrect.
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C. As mitotic CDK activity declines in late mitosis, cdc14 phosphatase activates APC/C by dephosphorylating Cdh1, thus promoting formation of APC/CCdh1.
Exit from mitosis requires a decrease in mitotic CDK activity (specifically CDK1/Cyclin B). This decline is initiated by the activation of the APC/C. The phosphatase cdc14 is activated in late mitosis and contributes to mitotic exit by dephosphorylating key substrates. One important substrate is Cdh1. Cdh1, when dephosphorylated, can bind to and activate the APC/C, forming the APC/CCdh1 complex. Active APC/CCdh1 then targets mitotic cyclins (Cyclin B) and S-phase cyclins for degradation, further reducing CDK activity and promoting the transition from mitosis into G1. This activation of APC/CCdh1 is crucial for maintaining the G1 state and preventing premature S-phase entry. Thus, this statement is correct.
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D. Securin keeps S-phase cyclins in inactive state till late G1.
Securin is a protein that inhibits the protease separase. Separase is responsible for cleaving the cohesin complexes that hold sister chromatids together. Degradation of securin by APC/CCdc20 in anaphase allows separase to become active, leading to sister chromatid separation and completion of mitosis. Securin's function is primarily related to anaphase progression and sister chromatid separation, not the regulation or inhibition of S-phase cyclins. S-phase cyclins are regulated by their synthesis and degradation, and their activity is controlled by binding to CDKs and by CDK inhibitors (CKIs) like p27 and p21. This statement is incorrect.
Identifying Correct Statements
Based on the analysis, statements A and C accurately describe mechanisms involved in regulating cell cycle progression in a way that impacts or facilitates the control of S-phase entry (by ensuring cyclins are degraded in G1 or activating the machinery that degrades them).
- Statement A correctly describes APC/C's role in degrading S-phase cyclins in G1.
- Statement C correctly describes how APC/CCdh1 is activated in late mitosis/G1, which is essential for keeping cyclin levels low.
Statements B and D are incorrect descriptions of cell cycle regulation.
Conclusion
The correct statements describing aspects related to the tight regulation of entry into S-phase are A and C.
Important Questions from Cell Division and Cell Cycle
Following statements were made about cell cycle regulation:
A. De novo synthesis and destruction of Cyclin B are essential for cell cycle progression in yeast.
B. De novo synthesis and destruction of Cyclin B and the related Cyclin dependent Kinase (CDK) are essential for cell cycle progression.
C. CDK activity is regulated by both activating and inhibitory phosphorylation.
D. Retinoblastoma (Rb) functions as an inhibitor of G2 to M transition.
E. Inactivation of Sic 1 is essential for transition into S phase.
Which one of the following represents the combination of the correct statements?
The table below lists cell cycle regulatory proteins and their known functions
Which one of the following options represents the correct match between cell cycle regulatory proteins with their known functions?Cell Cycle regu latory proteins Function A Cdk-activating kinase (CAK) (i) Suppresses G1/S-Cdk and S-Cdk activation in G1; helps cells withdraw from cell cycle when they terminally differentiate; phosphorylation by Cdk2 triggers its ubiquitylation by SCF. B Wee1 kinase (ii) Suppresses G1/S-Cdk and S-Cdk activities following DNA damage C p27 (mammals) (iii) Phosphorylates inhibitory sites in Cdks: primarily involved in suppressing Cdk1 activity before mitosis D p21 (mammals) (iv) Phosphorylates an activating site in Cdks Following statements were made about the characteristics of cyclin proteins:
A. Synthesis of M-cyclin is dependent on the cyclin mRNA that is newly transcribed after every cycle.
B. Destruction of M-cyclin toward the end of mitosis is driven by ubiquitin independent proteolytic system.
C. G1 cyclins can be activated by mitogenic factors.
D. Retinoblastoma (Rb) is a key target of the activated cyclin D - Cdk 4/6 complex.
E. While cyclin A1 expression is ubiquitous, cyclin A2 expression is restricted to the germ cell lineages.
Which one of the following options contains a combination of all correct statements?
To test the impact of cAMP on protein kinase A conformation in cells, an investigator made FRET biosensor by fusing two fluorescent proteins at the N-and C-terminus of protein kinase A. In the absence of cAMP in the cellular milieu, no FRET signal was detected. However, upon cAMP addition, a strong emission at 530 nm was observed. What could be the best configuration of fluorophores that were used by the investigator?
Given below are a few steps in clathrin‐coated vesicle formation in the secretory pathway.
(A) Receptor‐ligand recognition and binding
(B) Recruitment of adapter protein and clathrin
(C) Vesicle formation
(D) Uncoating of clathrin coats
Choose the option that correctly identifies the sequence of events in making a clathrin‐coated vesicle.
