S phase
Encyclopedia
S-phase is the part of the cell cycle
in which DNA
is replicated
, occurring between G1 phase
and G2 phase
. Precise and accurate DNA replication
is necessary to prevent genetic abnormalities which often lead to cell death or disease. Due to the importance, the regulatory pathways that govern this event in eukaryotes are highly conserved. This conservation makes the study of S-phase in model organisms such as Xenopus laevis embryos and budding yeast relevant to higher organisms.
is not major checkpoint in the regulation of the cell cycle
. Depending on levels of nutrients, energy and external factors, cells must decide to enter the cell cycle or move into a non-dividing state known as G0 phase
. This transition, as with all of the major checkpoint transitions in the cell cycle, is signaled by cyclins and cyclin dependent kinase (CDKs). The pulse of G1/S cyclins causes CLN3
-Cdk1
to activate Cln1/2, (Start point (yeast)
) as well as Clb5/6 at the initiation of S-phase. This pathway contains 2 positive feedback loops, allowing for rapid, unidirectional movement into S-phase. Redundant pathways like this are not uncommon because they allow for tuning the output of the system and often lead to faster genetic evolution.
. The goal of this process is to create exactly two identical semi-conserved chromosomes. The cell prevents more than one replication from occurring by loading pre-replication complexes onto the DNA at replication origins during G1-phase which are dismantled in S-phase as replication begins. In budding yeast, Cdc6
is degraded, Orc2/6 are phosphorylated and mcm proteins are excluded from the nucleus, preventing re-attachment of the replication machinery (DNA polymerase) to the DNA after initiation. Incredibly, DNA synthesis can occur as fast as 100 nucleotides/second and must be as accurate as 1 wrong base in 109 nucleotide additions.
comes upon damaged DNA, ATR
, a protein kinase, is activated. This kinase initiates several complex downstream pathways causing a halt in the initiation of new replication origins, prevention of mitosis and replication fork stabilization in order to keep the replication bubble open and DNA polymerase
complex attached while the damage is being fixed.
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
in which DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
is replicated
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
, occurring between G1 phase
G1 phase
The G1 phase is a period in the cell cycle during interphase, before the S phase. For many cells, this phase is the major period of cell growth during its lifespan. During this stage new organelles are being synthesized, so the cell requires both structural proteins and enzymes, resulting in great...
and G2 phase
G2 phase
G2 phase is the 3rd and final subphase of Interphase in the cell cycle directly preceding Mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated...
. Precise and accurate DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
is necessary to prevent genetic abnormalities which often lead to cell death or disease. Due to the importance, the regulatory pathways that govern this event in eukaryotes are highly conserved. This conservation makes the study of S-phase in model organisms such as Xenopus laevis embryos and budding yeast relevant to higher organisms.
S Phase Regulation
The G1/S transitionG1/S transition
The G1/S transition is a stage in the cell cycle at the boundary between the G1 phase and the S phase.It is a "point of no return" beyond which the cell is committed to dividing; in yeast this is called START and in multicellular eukaryotes it is termed the restriction point....
is not major checkpoint in the regulation of the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
. Depending on levels of nutrients, energy and external factors, cells must decide to enter the cell cycle or move into a non-dividing state known as G0 phase
G0 phase
The G0 phase is a period in the cell cycle in which cells exist in a quiescent state. G0 phase is viewed as either an extended G1 phase, where the cell is neither dividing nor preparing to divide, or a distinct quiescent stage that occurs outside of the cell cycle...
. This transition, as with all of the major checkpoint transitions in the cell cycle, is signaled by cyclins and cyclin dependent kinase (CDKs). The pulse of G1/S cyclins causes CLN3
CLN3
Battenin is a protein that in humans is encoded by the CLN3 gene located on chromosome 16.- Function :Battenin is involved in lysosomal function. Many alternatively spliced transcript variants have been found for this gene.-Clinical significance:...
-Cdk1
Cdk1
Cyclin dependent kinase 1 also known as Cdk1 or cell division control protein 2 homolog is a highly conserved protein that functions as a serine/threonine kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S....
to activate Cln1/2, (Start point (yeast)
Start point (yeast)
The Start checkpoint is a major cell cycle checkpoint in yeast. The Start checkpoint ensures irreversible cell-cycle entry even if conditions later become unfavorable. The physiological factors that control passage through the Start checkpoint include external nutrient concentrations, presence of...
) as well as Clb5/6 at the initiation of S-phase. This pathway contains 2 positive feedback loops, allowing for rapid, unidirectional movement into S-phase. Redundant pathways like this are not uncommon because they allow for tuning the output of the system and often lead to faster genetic evolution.
DNA Replication
The major event in S-phase is DNA replicationDNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. The goal of this process is to create exactly two identical semi-conserved chromosomes. The cell prevents more than one replication from occurring by loading pre-replication complexes onto the DNA at replication origins during G1-phase which are dismantled in S-phase as replication begins. In budding yeast, Cdc6
Cdc6
Cdc6, or Cell Division Cycle 6, is a protein in eukaryotic cells that is studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate...
is degraded, Orc2/6 are phosphorylated and mcm proteins are excluded from the nucleus, preventing re-attachment of the replication machinery (DNA polymerase) to the DNA after initiation. Incredibly, DNA synthesis can occur as fast as 100 nucleotides/second and must be as accurate as 1 wrong base in 109 nucleotide additions.
DNA Damage
Damage to DNA is detected and fixed during S-phase. When the replication forkReplication fork
The replication fork is a structure that forms within the nucleus during DNA replication. It is created by helicases, which break the hydrogen bonds holding the two DNA strands together. The resulting structure has two branching "prongs", each one made up of a single strand of DNA...
comes upon damaged DNA, ATR
ATR
ATR is an Italian-French aircraft manufacturer headquartered on the grounds of Toulouse Blagnac International Airport in Blagnac, France surburb of Toulouse. It was formed in 1981 by Aérospatiale of France and Aeritalia of Italy...
, a protein kinase, is activated. This kinase initiates several complex downstream pathways causing a halt in the initiation of new replication origins, prevention of mitosis and replication fork stabilization in order to keep the replication bubble open and DNA polymerase
DNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
complex attached while the damage is being fixed.
See also
- S phase index (SPI)
- S-fraction or S-phase fraction (oncology/pathology prognosis)