Cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.
This article is about the eukaryotic cell cycle. For the prokaryotic cell cycle, see fission (biology). For the separation of chromosomes that occurs as part of the cell cycle, see mitosis. For the academic journal, see Cell Cycle (journal).
In eukaryotic cells (having a cell nucleus) including animal, plant, fungal, and protist cells, the cell cycle is divided into two main stages: interphase, and the M phase that includes mitosis and cytokinesis.[1] During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the M phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps of the cycle that determine if the cell can progress to the next phase.
In cells without nuclei the prokaryotes, bacteria and archaea, the cell cycle is divided into the B, C, and D periods. The B period extends from the end of cell division to the beginning of DNA replication. DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the splitting of the bacterial cell into two daughter cells.[2]
In single-celled organisms, a single cell-division cycle is how the organism reproduces to ensure it's survival. In multicellular organisms such as plants and animals, a series of cell-division cycles is how the organism develops from a single-celled fertilized egg into a mature organism, and is also the process by which hair, skin, blood cells, and some internal organs are regenerated and healed (with possible exception of nerves; see nerve damage). After cell division, each of the daughter cells begin the interphase of a new cell cycle. Although the various stages of interphase are not usually morphologically distinguishable, each phase of the cell cycle has a distinct set of specialized biochemical processes that prepare the cell for initiation of the cell division.
Role in tumor formation[edit]
A disregulation of the cell cycle components may lead to tumor formation.[52] As mentioned above, when some genes like the cell cycle inhibitors, RB, p53 etc. mutate, they may cause the cell to multiply uncontrollably, forming a tumor. Although the duration of cell cycle in tumor cells is equal to or longer than that of normal cell cycle, the proportion of cells that are in active cell division (versus quiescent cells in G0 phase) in tumors is much higher than that in normal tissue.[53] Thus there is a net increase in cell number as the number of cells that die by apoptosis or senescence remains the same.
The cells which are actively undergoing cell cycle are targeted in cancer therapy as the DNA is relatively exposed during cell division and hence susceptible to damage by drugs or radiation. This fact is made use of in cancer treatment; by a process known as debulking, a significant mass of the tumor is removed which pushes a significant number of the remaining tumor cells from G0 to G1 phase (due to increased availability of nutrients, oxygen, growth factors etc.). Radiation or chemotherapy following the debulking procedure kills these cells which have newly entered the cell cycle.[15]
The fastest cycling mammalian cells in culture, crypt cells in the intestinal epithelium, have a cycle time as short as 9 to 10 hours. Stem cells in resting mouse skin may have a cycle time of more than 200 hours. Most of this difference is due to the varying length of G1, the most variable phase of the cycle. M and S do not vary much.
In general, cells are most radiosensitive in late M and G2 phases and most resistant in late S phase. For cells with a longer cell cycle time and a significantly long G1 phase, there is a second peak of resistance late in G1. The pattern of resistance and sensitivity correlates with the level of sulfhydryl compounds in the cell. Sulfhydryls are natural substances that protect cells from radiation damage and tend to be at their highest levels in S and at their lowest near mitosis.
Homologous recombination (HR) is an accurate process for repairing DNA double-strand breaks. HR is nearly absent in G1 phase, is most active in S phase, and declines in G2/M.[54] Non-homologous end joining, a less accurate and more mutagenic process for repairing double strand breaks, is active throughout the cell cycle.
Cell cycle evolution[edit]
Evolution of the genome[edit]
The cell cycle must duplicate all cellular constituents and equally partition them into two daughter cells. Many constituents, such as proteins and ribosomes, are produced continuously throughout the cell cycle (except during M-phase). However, the chromosomes and other associated elements like MTOCs, are duplicated just once during the cell cycle. A central component of the cell cycle is its ability to coordinate the continuous and periodic duplications of different cellular elements, which evolved with the formation of the genome.
The pre-cellular environment contained functional and self-replicating RNAs.[55] All RNA concentrations depended on the concentrations of other RNAs that might be helping or hindering the gathering of resources. In this environment, growth was simply the continuous production of RNAs. These pre-cellular structures would have had to contend with parasitic RNAs, issues of inheritance, and copy-number control of specific RNAs.[55][56]
Partitioning "genomic" RNA from "functional" RNA helped solve these problems.[57] The fusion of multiple RNAs into a genome gave a template from which functional RNAs were cleaved. Now, parasitic RNAs would have to incorporate themselves into the genome, a much greater barrier, in order to survive. Controlling the copy number of genomic RNA also allowed RNA concentration to be determined through synthesis rates and RNA half-lives, instead of competition.[55] Separating the duplication of genomic RNAs from the generation of functional RNAs allowed for much greater duplication fidelity of genomic RNAs without compromising the production of functional RNAs. Finally, the replacement of genomic RNA with DNA, which is a more stable molecule, allowed for larger genomes. The transition from self-catalysis enzyme synthesis to genome-directed enzyme synthesis was a critical step in cell evolution, and had lasting implications on the cell cycle, which must regulate functional synthesis and genomic duplication in very different ways.[55]
Cyclin-dependent kinase and cyclin evolution[edit]
Cell-cycle progression is controlled by the oscillating concentrations of different cyclins and the resulting molecular interactions from the various cyclin-dependent kinases (CDKs). In yeast, just one CDK (Cdc28 in S. cerevisiae and Cdc2 in S. pombe) controls the cell cycle.[58] However, in animals, whole families of CDKs have evolved.[59][60] Cdk1 controls entry to mitosis and Cdk2, Cdk4, and Cdk6 regulate entry into S phase. Despite the evolution of the CDK family in animals, these proteins have related or redundant functions.[61][62][63] For example, cdk2 cdk4 cdk6 triple knockout mice cells can still progress through the basic cell cycle.[64] cdk1 knockouts are lethal, which suggests an ancestral CDK1-type kinase ultimately controlling the cell cycle.[64]
Arabidopsis thaliana has a Cdk1 homolog called CDKA;1, however cdka;1 A. thaliana mutants are still viable,[65] running counter to the opisthokont pattern of CDK1-type kinases as essential regulators controlling the cell cycle.[66] Plants also have a unique group of B-type CDKs, whose functions may range from development-specific functions to major players in mitotic regulation.[67][68]
This article incorporates from Science Primer. NCBI. Archived from the original on 8 December 2009.
