Cell Cycle and Interphase
Cell cycle is the sequential process taking place to regulate the growth of organism; cell divides to produce a genetic replica and enters the stage of cell growth.
Cell growth involves the synthesis of organic material and integrates information across its counter parts for synchronous development of the whole body.
The cell synthesis phase lasts till a cell reaches its maturity; on initiation the cell again divides to produce new cell and the process continues.
Cell cycle is a sequential development of cell between two cell divisions.
The cycle is genetically controlled and are programmed in every cell and are specific for each region. Varied species has variable time length of cell cycle decided by physiological and influences pertaining to their niche.
Two Phases of cell cycle are: INTERPHASE and MITOTIC PHASE.
INTERPHASE involves G1, synthesis and G2 phase; chromosomal replication and development is regulated by the phase; determines the quality and quantity of chromosome entering the daughter cells and a balance is maintained by the phase.
Karyokinesis and Cytokinesis division, segregation of chromosome and cell takes place during MITOTIC PHASE.
The notable feature of cell cycle is eukaryotic organisms though diverse and distinct have a common type of cell division over the Kingdom of Eukaryotes is a scientific wonder and research have emphasized that timing of a cell entering the cell cycle is essential in cell cycle regulation.
Interphase of the cell cycle is non dividing phase where the cells undergo major synthesis and other integrating functions transducing signals and coordinate with other cells to produce an overall reaction to the stimulus.
Biosynthetic activity is more prevalent in this phase; absence of cell division marks a resting period; varies for every differentiated cells.
Certain cells might have a short resting period and certain cells such as neurons loses the power of differentiation and remains constant.
I. Gap1 Phase
The first gap phase starts just after the 2 daughter cells formed by mitosis is long and are species specific.
Intermediate to Mitosis and the synthesis phase the cell increases in size by synthesizing proteins and RNA for Synthesis Phase.
In a cell cycle, G1 phase is regulated by the external and internal factors.
External limiting factor is the availability of the nutrients in general eukaryotic organism and additional hormonal induction in plants.
Most of the organism restrict their cycle at G1 or enter G0, few cells on proper hormonal induction will reenter the cell cycle from G0 phase; specifically, plants have a specialized region called the meristem which continuously divide to produce cell growth.
The G1 phase determines the fate of the cell whether to enter cell cycle or to retain in G1 phase.
The cell must grow to an appropriate size and must synthesize proteins and RNA to enter S phase, and this is regulated by Cyclins and CDK’s.
II. Synthesis Phase
The threshold point – restriction point in mammals and START in other organisms; when crossed the cells enter the synthesis phase.
The G1 phase prepared the cell and its components to synthesis phase to get committed to cell division.
The cell division is arrested when external aids are less or unavailable.
The DNA replication doubles the genetic material, but the chromosome is not condensed and replicated material remains as chromatin.
Synthesis of genetic material is significant in this phase where cells are committed to divide and produce 2 daughter cells in most of the metazoans.
The S phase does not induce the increase in chromosomal numbers but doubles the genetic material.
Endoreduplication a landmark in plant endosperm is the different process of the metazoans permits DNA replication without mitosis results in ploidy. In animals, Drosophila’s salivary glands and mammal’s hepatocytes exhibit endoreplication.
Synthesis phase and Mitosis phase is separated by G2 Phase; marked by absence of synthetic function.
This phase is a preparatory phase where the cell again enters the mitotic cycle for division.
Decondensed chromatin starts a preliminary condensation marks the start of mitotic phase.
Condensation inhibits the RNA synthesis gradually as the synthesis sites are being compactly wound for replication.
G2 Phase has minimal RNA synthesis which reduces or absent in Mitotic phase.
Interphase Checkpoints and Regulation
The cell enters cell cycle to divide and produce daughter cells or it participates in regular metabolic function is determined during the interphase.
The process becomes irreversible when the cells traverse across G1 phase and enters S phase.
Determination and commitment to cell division is regulated by protein kinases CDK – CYC complex which are conserved in plants but varies across other kingdoms; are heteromeric proteins which are predominant in eukaryotic cells determines the fate of cell based on the internal and external cues.
Each transition from stages is regulated and governed by CYC – CDK complex; involves an intricate network of mechanism involves positive and negative regulation of many numbers of components to maintain a homeostasis.
Stages of cell cycle also provides checkpoint to make sure the proper functioning of the cell cycle.
G1/S Cell Cycle Checkpoints
G1 phase is the lap phase where the cell obtains essential growth and necessary elements; increase in size by biomolecular synthesis; to proceed the cell cycle or to enter G0 to restrict them by functioning regular metabolic activities.
In most of the eukaryotes the increase in CDKA – CYCD in G1 phase makes the cell cross the restriction point and irreversibly committed to cell cycle; involves an activation pathway.
The Cyclin D concentration responds to external cues such as hormone induction, availabilities of nutrients; promote CDKA-CYCD complex thereby initiating the G1 activity; the concentration of the CYCD-CDKA complex increase the phosphorylation of Rb (Retinoblastoma) proteins.
The Rb proteins are the inhibitor of transcription factors transcribing the proteins and RNA essential for the synthesis phase.
In the absence of the CYC-CDK complex the pathway is inhibited by Rb protein.
The transcription is also inhibited when a cell synthesis the essential quantity of proteins required for S Phase or when the CYC-CDK complex over express in the process.
The transition pathway is conserved in plants. Generally; plants have a single Rb homologue and 6 types of E2F transcription factors.
E2F is further divided into 2 groups: CANONICAL and ATYPICAL. E2Fa, E2Fb, E2Fc require a dimeric substance such as DP to bind to the DNA are canonical and monomeric factors E2Fd, E2Fe, E2Ff are Atypical.
Each E2F factors has a definitive function which are not yet determined correctly; but from many scientific experiments in Arabidopsis the functions are deduced as:
E2Fa – Transcriptional
E2Fb – Transcriptional
E2Fc – Down Regulation of Transcription (Repressors)
E2Fd – unidentified
E2Fe – Prevent endocycles delaying cell elongation
E2Ff – Cell expansion Also, E2Fa and E2Fb are more essential in S Phase to balance proliferation and endoreduplication in cell.
E2F transcription leads to initiation and increase in the DNA replication by setting up a replication origin where ORC – origin replication complex binds to produce the replicating fork for DNA synthesis.
The regulating checkpoint in the process is the expression of E2Fc transcriptional factors which are induced by the genetic expression mediated by E2Fa/b; inhibit the over expression of DNA Replication.
G2/M Cell Cycle Checkpoints
The transition of the particular phase involves many genes and transcriptional factors in cycle progression.
The transcriptional factors are of 5 types: MYB3R1, MYB3R2, MYB3R3, MYB3R4 and MYB3R5.
The G2/M transition involves proteins which are also present in M phase induces cytokinesis.
The functions of transcriptional Factors are:
MYB3R2 – circadian clock
MYB3R1, MYB3R4 – activates the gene expression
MYB3R3, MYB3R5 – repress the gene expression
MYB3R3 and 5 regulates the function of gene expression of G2/M phase when it over express.
Along with this; APC/C – Anaphase promoting complex/Cyclosomes targets the proteolysis which regulates the G2/M transition and supports Mitosis phase of cell proliferation.
- Functional organisation of the genome during interphase. Curr Opin Genet Dev . 2007 Oct;17(5):451-5.
- Interphase cytogenetics and its role in molecular diagnostics of solid tumors. Am J Pathol . 1998 Feb;152(2):325-7.
- Interphase cytogenetics: at the interface of genetics and morphology. Anal Cell Pathol . 1999;19(1):3-6.
- Chromosome topology in mammalian interphase nuclei. Exp Cell Res . 1991 Feb;192(2):325-32.
- Two-step interphase microtubule disassembly aids spindle morphogenesis. BMC Biol . 2018 Jan 23;16(1):14.
- Interphase microtubules: chief casualties in the war on cancer? Drug Discov Today . 2014 Jul;19(7):824-9.
- Interphase Cell Cycle Staging using Deep Learning. Annu Int Conf IEEE Eng Med Biol Soc . 2020 Jul;2020:1432-1435.