Cell cycle

For the separation of chromosomes that occurs as part of period extends from the end of cell division to the begin-
the cell cycle, see mitosis. For the Academic journal, see ning of DNA replication. DNA replication occurs during
Cell Cycle (journal). the C period. The D period refers to the stage between the
See also: Cell division end of DNA replication and the splitting of the bacterial
The cell cycle or cell-division cycle is the series of events cell into two daughter cells.[2] In cells with a nucleus, as
in eukaryotes, the cell cycle is also divided into three pe-
riods: interphase, the mitotic (M) phase, and cytokinesis.
During interphase, the cell grows, accumulating nutrients
needed for mitosis, preparing it for cell division and du-
plicating its DNA. During the mitotic phase, the cell splits
itself into two distinct daughter cells. During the final
stage, cytokinesis, the new cell is completely divided. To
ensure the proper division of the cell, there are control
mechanisms known as cell cycle checkpoints.
The cell-division cycle is a vital process by which a single-
celled fertilized egg develops into a mature organism, as
well as the process by which hair, skin, blood cells, and
some internal organs are renewed. After cell division,
each of the daughter cells begin the interphase of a new
cycle. Although the various stages of interphase are not
usually morphologically distinguishable, each phase of
the cell cycle has a distinct set of specialized biochem-
ical processes that prepare the cell for initiation of cell
division.
Schematic of the cell cycle. outer ring: I = Interphase, M =
Mitosis; inner ring: M = Mitosis, G1 = Gap 1, G2 = Gap 2,
S = Synthesis; not in ring: G0 = Gap 0/Resting.[1] 1 Cell cycle phases

1.1 G0 phase

Onion (Allium) cells in different phases of the cell cycle. Growth

in an organism is carefully controlled by regulating the cell cycle.

that take place in a cell leading to its division and du-

plication of its DNA (DNA replication) to produce two Plant cell cycle
daughter cells. In bacteria, which lack a cell nucleus, the
cell cycle is divided into the B, C, and D periods. The B The word “post-mitotic” is sometimes used to refer to

1
2 1 CELL CYCLE PHASES

phase, resume at a high rate. The duration of G1 is highly

variable, even among different cells of the same species.
In this phase, the cell increases its supply of proteins, in-
creases the number of organelles (such as mitochondria,
ribosomes), and grows in size.

1.2.2 S Phase

The ensuing S phase starts when DNA replication com-

mences; when it is completed, all of the chromosomes
have been replicated, i.e., each chromosome has two (sis-
ter) chromatids. Thus, during this phase, the amount of
DNA in the cell has effectively doubled, though the ploidy
of the cell remains the same. During this phase, synthe-
sis is completed as quickly as possible due to the exposed
base pairs being sensitive to harmful external factors such
as mutagens.
Animal cell cycle
1.3 Mitotic phase
both quiescent and senescent cells. Nonproliferative cells
in multicellular eukaryotes generally enter the quiescent Main article: Mitosis
G0 state from G1 and may remain quiescent for long pe-
riods of time, possibly indefinitely (as is often the case The relatively brief M phase consists of nuclear division
for neurons). This is very common for cells that are (karyokinesis). It is a relatively short period of the cell
fully differentiated. Cellular senescence occurs in re- cycle. M phase is complex and highly regulated. The
sponse to DNA damage or degradation that would make sequence of events is divided into phases, corresponding
a cell’s progeny nonviable; for example, become cancer- to the completion of one set of activities and the start of
ous. Some cells enter the G0 phase semi-permanently the next. These phases are sequentially known as:
e.g., some liver, kidney, stomach cells. Many cells do not
enter G0 and continue to divide throughout an organism’s • prophase,
life, e.g. epithelial cells.
• metaphase,
• anaphase,
1.2 Interphase
• telophase
Before a cell can enter cell division, it needs to take in
nutrients. All of the preparations are done during inter- • cytokinesis (strictly speaking, cytokinesis is not part
phase. Interphase is a series of changes that takes place of mitosis but is an event that directly follows mito-
in a newly formed cell and its nucleus, before it becomes sis in which cytoplasm is divided into two daughter
capable of division again. It is also called preparatory cells)
phase or intermitosis. Previously it was called resting
stage because there is no apparent activity related to cell Mitosis is the process by which a eukaryotic cell separates
division.Typically interphase lasts for at least 90% of the the chromosomes
[3]
in its cell nucleus into two identical sets
total time required for the cell cycle. in two nuclei. During the process of mitosis the pairs of
chromosomes condense and attach to fibers that pull the
Interphase proceeds in three stages, G1 , S, and G2 , pre- sister chromatids to opposite sides of the cell.[4] It is gen-
ceded by the previous cycle of mitosis and cytokinesis. erally followed immediately by cytokinesis, which divides
The cell’s nuclear chromosomes are duplicated during S the nuclei, cytoplasm, organelles and cell membrane into
phase. two cells containing roughly equal shares of these cellular
components. Mitosis and cytokinesis together define the
mitotic (M) phase of the cell cycle – the division of the
1.2.1 G1 Phase
mother cell into two daughter cells, genetically identical
The first phase within interphase, from the end of the pre- to each other and to their parent cell. This accounts for
vious M phase until the beginning of DNA synthesis, is approximately 10% of the cell cycle.
called G1 (G indicating gap). It is also called the growth Mitosis occurs exclusively in eukaryotic cells, but oc-
phase. During this phase, the biosynthetic activities of curs in different ways in different species. For ex-
the cell, which are considerably slowed down during M ample, animals undergo an “open” mitosis, where the
2.1 Role of cyclins and CDKs 3

nuclear envelope breaks down before the chromosomes

separate, while fungi such as Aspergillus nidulans and
Saccharomyces cerevisiae (yeast) undergo a “closed” mi-
tosis, where chromosomes divide within an intact cell nu-
cleus.[5] Prokaryotic cells, which lack a nucleus, divide by
a process called binary fission.
Because cytokinesis usually occurs in conjunction with
mitosis, “mitosis” is often used interchangeably with “M
phase”. However, there are many cells where mito-
sis and cytokinesis occur separately, forming single cells
with multiple nuclei in a process called endoreplication.
This occurs most notably among the fungi and slime
moulds, but is found in various groups. Even in ani-
mals, cytokinesis and mitosis may occur independently,
for instance during certain stages of fruit fly embryonic
development.[6] Errors in mitosis can either kill a cell
through apoptosis or cause mutations that may lead to
cancer.

2 Regulation of eukaryotic cell cy-

cle
Regulation of the cell cycle involves processes crucial to Nobel Laureate Paul Nurse
the survival of a cell, including the detection and repair of
genetic damage as well as the prevention of uncontrolled constitutively expressed in cells whereas cyclins are syn-
cell division. The molecular events that control the cell thesised at specific stages of the cell cycle, in response to
cycle are ordered and directional; that is, each process various molecular signals.[10]
occurs in a sequential fashion and it is impossible to “re-
verse” the cycle.
2.1.1 General mechanism of cyclin-CDK interac-
tion
2.1 Role of cyclins and CDKs
Upon receiving a pro-mitotic extracellular signal, G1
Two key classes of regulatory molecules, cyclins and cyclin-CDK complexes become active to prepare the cell
cyclin-dependent kinases (CDKs), determine a cell’s for S phase, promoting the expression of transcription
progress through the cell cycle.[7] Leland H. Hartwell, R. factors that in turn promote the expression of S cyclins
Timothy Hunt, and Paul M. Nurse won the 2001 Nobel and of enzymes required for DNA replication. The G1
Prize in Physiology or Medicine for their discovery of cyclin-CDK complexes also promote the degradation of
these central molecules.[8] Many of the genes encoding molecules that function as S phase inhibitors by targeting
cyclins and CDKs are conserved among all eukaryotes, them for ubiquitination. Once a protein has been ubiq-
but in general more complex organisms have more elabo- uitinated, it is targeted for proteolytic degradation by the
rate cell cycle control systems that incorporate more indi- proteasome. However, results from a recent study of E2F
vidual components. Many of the relevant genes were first transcriptional dynamics at the single-cell level argue that
identified by studying yeast, especially Saccharomyces the role of G1 cyclin-CDK activities, in particular cyclin
cerevisiae;[9] genetic nomenclature in yeast dubs many of D-CDK4/6, is to tune the timing rather than the commit-
these genes cdc (for “cell division cycle”) followed by an ment of cell cycle entry.[11]
identifying number, e.g. cdc25 or cdc20. Active S cyclin-CDK complexes phosphorylate proteins
Cyclins form the regulatory subunits and CDKs the cat- that make up the pre-replication complexes assembled
alytic subunits of an activated heterodimer; cyclins have during G1 phase on DNA replication origins. The phos-
no catalytic activity and CDKs are inactive in the absence phorylation serves two purposes: to activate each already-
of a partner cyclin. When activated by a bound cyclin, assembled pre-replication complex, and to prevent new
CDKs perform a common biochemical reaction called complexes from forming. This ensures that every portion
phosphorylation that activates or inactivates target pro- of the cell’s genome will be replicated once and only once.
teins to orchestrate coordinated entry into the next phase The reason for prevention of gaps in replication is fairly
of the cell cycle. Different cyclin-CDK combinations clear, because daughter cells that are missing all or part
determine the downstream proteins targeted. CDKs are of crucial genes will die. However, for reasons related to
4 2 REGULATION OF EUKARYOTIC CELL CYCLE

Chemokines,

gene copy number effects, possession of extra copies of Survival Factors

(e.g., IGF1)
Hormones,
Transmitters
(e.g., interleukins,
Growth Factors
(e.g., TGFα, EGF)
Extracellular
Matrix
serotonin, etc.)

certain genes is also deleterious to the daughter cells.

GPCR
Integrins
RTK RTK
Mitotic cyclin-CDK complexes, which are synthesized PLC Grb2/SOS
cdc42
Fyn/Shc
Wnt

Frizzled
but inactivated during S and G2 phases, promote the ini- PI3K

Akt
PKC
G-Protein

Adenylate
Ras

Raf
FAK
Src
Dishevelled

GSK-3β

tiation of mitosis by stimulating downstream proteins in- Akkα cyclase MEK

Hedgehog

Cytokine Receptor
NF-κB APC
PKA MEKK MAPK MKK
Cytokines IκB β-catenin

volved in chromosome condensation and mitotic spin-

Patched
JAKs
(e.g., EPC)
STAT3,5 TCF
Myc: Mad:

dle assembly. A critical complex activated during this

ERK JNKs β-catenin:TCF
Bcl-xL Max Max
Fos Jun

SMO
Cytochrome C CREB CycID Gli

process is a ubiquitin ligase known as the anaphase- Caspase 9

Rb CDK4

E2F
p16
p15
Gene Regulation
promoting complex (APC), which promotes degradation Caspase 8 Apoptosis
ARF
CyclE
CDK2
p27

p21
Cell
of structural proteins associated with the chromosomal FADD
Bad
Bcl-2
Mt Bax
mdm2
p53
Proliferation

kinetochore. APC also targets the mitotic cyclins for

Abnormality
FasR Sensor Bim

degradation, ensuring that telophase and cytokinesis can Death factors

proceed.[12]
(e.g. FasL, Tnf)

Overview of signal transduction pathways involved in apoptosis,

2.1.2 Specific action of cyclin-CDK complexes also known as “programmed cell death”.

Cyclin D is the first cyclin produced in the cell cycle,

to radiation). p27 is activated by Transforming Growth
in response to extracellular signals (e.g. growth factors).
Factor of β (TGF β), a growth inhibitor.
Cyclin D binds to existing CDK4, forming the active cy-
clin D-CDK4 complex. Cyclin D-CDK4 complex in turn The INK4a/ARF family includes p16INK4a , which binds
phosphorylates the retinoblastoma susceptibility protein to CDK4 and arrests the cell cycle in G1 phase, and
(Rb). The hyperphosphorylated Rb dissociates from the p14ARF which prevents p53 degradation.
E2F/DP1/Rb complex (which was bound to the E2F re- Synthetic inhibitors of Cdc25 could also be useful for the
sponsive genes, effectively “blocking” them from tran- arrest of cell cycle and therefore be useful as antineoplas-
scription), activating E2F. Activation of E2F results in tic and anticancer agents.[14]
transcription of various genes like cyclin E, cyclin A,
DNA polymerase, thymidine kinase, etc. Cyclin E thus
produced binds to CDK2, forming the cyclin E-CDK2 2.3 Transcriptional regulatory network
complex, which pushes the cell from G1 to S phase (G1 /S,
which initiates the G2 /M transition).[13] Cyclin B-cdk1 Current evidence suggests that a semi-autonomous tran-
complex activation causes breakdown of nuclear enve- scriptional network acts in concert with the CDK-cyclin
lope and initiation of prophase, and subsequently, its de- machinery to regulate the cell cycle. Several gene expres-
activation causes the cell to exit mitosis.[10] sion studies in Saccharomyces cerevisiae have identified
A recent quantitative study of E2F transcriptional dynam- 800-1200 genes that change expression over the course of
ics at the single-cell level by using engineered fluorescent the cell cycle.[9][15][16] They are transcribed at high levels
reporter cells proposed an alternative model for interpret- at specific points in the cell cycle, and remain at lower
ing the control of cell cycle entry. Genes that regulate levels throughout the rest of the cycle. While the set of
the amplitude of E2F accumulation, such as Myc, de- identified genes differs between studies due to the compu-
termine the commitment into cell cycle and S phase en- tational methods and criteria used to identify them, each
try. G1 cyclin-CDK activities are not the driver of cell study indicates that a large portion of yeast genes are tem-
cycle entry. Instead, they primarily tune the timing of porally regulated.[17]
E2F increase, thereby modulating the pace of cell cycle Many periodically expressed genes are driven by
progression.[11] transcription factors that are also periodically expressed.
One screen of single-gene knockouts identified 48
transcription factors (about 20% of all non-essential
2.2 Inhibitors transcription factors) that show cell cycle progression
defects.[18] Genome-wide studies using high throughput
Two families of genes, the cip/kip (CDK interacting pro- technologies have identified the transcription factors that
tein/Kinase inhibitory protein) family and the INK4a/ARF bind to the promoters of yeast genes, and correlating these
(Inhibitor of Kinase 4/Alternative Reading Frame) fam- findings with temporal expression patterns have allowed
ily, prevent the progression of the cell cycle. Because the identification of transcription factors that drive phase-
these genes are instrumental in prevention of tumor for- specific gene expression.[15][19] The expression profiles of
mation, they are known as tumor suppressors. these transcription factors are driven by the transcription
The cip/kip family includes the genes p21, p27 and p57. factors that peak in the prior phase, and computational
They halt cell cycle in G1 phase, by binding to, and inac- models have shown that a CDK-autonomous network of
tivating, cyclin-CDK complexes. p21 is activated by p53 these transcription factors is sufficient to produce steady-
(which, in turn, is triggered by DNA damage e.g. due state oscillations in gene expression).[16][20]
 5

Experimental evidence also suggests that gene expression Cell cycle checkpoints are used by the cell to monitor and
can oscillate with the period seen in dividing wild-type regulate the progress of the cell cycle.[28] Checkpoints
cells independently of the CDK machinery. Orlando et prevent cell cycle progression at specific points, allowing
al. used microarrays to measure the expression of a set verification of necessary phase processes and repair of
of 1,271 genes that they identified as periodic in both wild DNA damage. The cell cannot proceed to the next phase
type cells and cells lacking all S-phase and mitotic cyclins until checkpoint requirements have been met. Check-
(clb1,2,3,4,5,6). Of the 1,271 genes assayed, 882 con- points typically consist of a network of regulatory pro-
tinued to be expressed in the cyclin-deficient cells at the teins that monitor and dictate the progression of the cell
same time as in the wild type cells, despite the fact that through the different stages of the cell cycle.
the cyclin-deficient cells arrest at the border between G1 There are several checkpoints to ensure that damaged
and S phase. However, 833 of the genes assayed changed
or incomplete DNA is not passed on to daughter cells.
behavior between the wild type and mutant cells, indicat- Three main checkpoints exist: the G1 /S checkpoint, the
ing that these genes are likely directly or indirectly reg-
G2 /M checkpoint and the metaphase (mitotic) check-
ulated by the CDK-cyclin machinery. Some genes that point. G1 /S transition is a rate-limiting step in the cell cy-
continued to be expressed on time in the mutant cells
cle and is also known as restriction point.[10] An alterna-
were also expressed at different levels in the mutant and tive model of the cell cycle response to DNA damage has
wild type cells. These findings suggest that while the tran- also been proposed, known as the postreplication check-
scriptional network may oscillate independently of the point.
CDK-cyclin oscillator, they are coupled in a manner that
requires both to ensure the proper timing of cell cycle p53 plays an important role in triggering the control
events.[16] Other work indicates that phosphorylation, a mechanisms at both G1 /S and G2 /M checkpoints.
post-translational modification, of cell cycle transcription
factors by Cdk1 may alter the localization or activity of
the transcription factors in order to tightly control timing
of target genes.[18][21][22]
4 Role in tumor formation
While oscillatory transcription plays a key role in the pro-
A disregulation of the cell cycle components may lead
gression of the yeast cell cycle, the CDK-cyclin machin-
to tumor formation.[29] As mentioned above, when some
ery operates independently in the early embryonic cell
genes like the cell cycle inhibitors, RB, p53 etc. mutate,
cycle. Before the midblastula transition, zygotic tran-
they may cause the cell to multiply uncontrollably, form-
scription does not occur and all needed proteins, such as
ing a tumor. Although the duration of cell cycle in tumor
the B-type cyclins, are translated from maternally loaded
cells is equal to or longer than that of normal cell cycle,
mRNA.[23]
the proportion of cells that are in active cell division (ver-
sus quiescent cells in G0 phase) in tumors is much higher
than that in normal tissue. Thus there is a net increase in
2.4 DNA replication and DNA replication cell number as the number of cells that die by apoptosis
origin activity or senescence remains the same.
The cells which are actively undergoing cell cycle are tar-
Analyses of synchronized cultures of Saccharomyces geted in cancer therapy as the DNA is relatively exposed
cerevisiae under conditions that prevent DNA replica- during cell division and hence susceptible to damage by
tion initiation without delaying cell cycle progression drugs or radiation. This fact is made use of in cancer
showed that origin licensing decreases the expression treatment; by a process known as debulking, a signifi-
of genes with origins near their 3' ends, revealing that cant mass of the tumor is removed which pushes a signif-
downstream origins can regulate the expression of up- icant number of the remaining tumor cells from G0 to G1
stream genes.[24] This confirms previous predictions from phase (due to increased availability of nutrients, oxygen,
mathematical modeling of a global causal coordination growth factors etc.). Radiation or chemotherapy follow-
between DNA replication origin activity and mRNA ing the debulking procedure kills these cells which have
expression,[25][26][27] and shows that mathematical mod- newly entered the cell cycle.[10]
eling of DNA microarray data can be used to correctly
The fastest cycling mammalian cells in culture, crypt cells
predict previously unknown biological modes of regula-
in the intestinal epithelium, have a cycle time as short as
tion.
9 to 10 hours. Stem cells in resting mouse skin may have
a cycle time of more than 200 hours. Most of this differ-
ence is due to the varying length of G1 , the most variable
3 Checkpoints phase of the cycle. M and S do not vary much.
In general, cells are most radiosensitive in late M and G2
Main article: Cell cycle checkpoint phases and most resistant in late S.
For cells with a longer cell cycle time and a significantly
6 6 REFERENCES

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vol. 15 (January 31 – February 4, 2004) http://www.
med.miami.edu/mnbws/documents/Alter-.pdf. Missing • Transcriptional program of the cell cycle: high-
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7 Further reading
• Morgan DO (2007). The Cell Cycle: Principles of
Control. London: Published by New Science Press
in association with Oxford University Press. ISBN
0-87893-508-8.

• Alberts B, Johnson A, Lewis J, Raff M, Roberts K,

Walter P (2008). “Chapter 17”. Molecular Biology
of the Cell (5th ed.). New York: Garland Science.
ISBN 978-0-8153-4111-6.
8 9 TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

9 Text and image sources, contributors, and licenses

9.1 Text
• Cell cycle Source: https://en.wikipedia.org/wiki/Cell_cycle?oldid=698588720 Contributors: AxelBoldt, Magnus Manske, Sodium, Karen
Johnson, Lexor, Deadstar, Nikki chan, Timc, Samsara, Chuunen Baka, Bearcat, Mwfn, Robbot, Ktotam, Hadal, GreatWhiteNortherner,
Alan Liefting, Dave6, Giftlite, Everyking, Dmb000006, Bensaccount, Guanaco, Alexf, Onco p53, Phe, Piotrus, Joyous!, Adashiel, D6,
Discospinster, Guanabot, Bender235, ESkog, JackWasey, Deicas, Jfraser, Arcadian, Ingolia, La goutte de pluie, VBGFscJUn3, MPerel,
Alansohn, Arthena, Sl, Fritzpoll, Dflanagan, Snowolf, Danhash, Tomash, Dan100, Mindmatrix, EnSamulili, Ruud Koot, Protox, MONGO,
Flamingspinach, Isnow, Prashanthns, Palica, GFP~enwiki, MassGalactusUniversum, Kissekatt, Sjö, Rjwilmsi, Jake Wartenberg, Sango123,
FlaBot, SchuminWeb, Vietbio~enwiki, RexNL, Spencerk, Scoops, John Dalton, Bgwhite, Whosasking, The Rambling Man, Wavelength,
Midgley, Reo On, Rsrikanth05, NawlinWiki, Snek01, Grafen, Kkmurray, JuJube, Heathhunnicutt, LeonardoRob0t, Jedi6, Allens, Grin-
Bot~enwiki, Hughitt1, SmackBot, Reedy, EncycloPetey, Delldot, Jab843, Zephyris, Yamaguchi , Gilliam, Jethero, Kurykh, Keegan,
Persian Poet Gal, Stevage, Deli nk, Ikiroid, Can't sleep, clown will eat me, Rrburke, Khoikhoi, Flyguy649, T-borg, VegaDark, AThing,
Kuru, Scientizzle, Jan.Smolik, SvenskaJohannes, Mgiganteus1, Shinryuu, Serephine, Mets501, Citicat, Lunajurai, Iridescent, 060128,
Igoldste, Tawkerbot2, Ghaly, Xcentaur, Alexei Kouprianov, Ale jrb, Rawling, Benwildeboer, Lave, Robinatron, Chasingsol, Tawkerbot4,
Epbr123, Opabinia regalis, Mojo Hand, Nezzadar, AgentPeppermint, Openlander, Drdaveng, TimVickers, Fayenatic london, Darklilac,
Thaerhashem, Zidane tribal, Figma, Erxnmedia, The Transhumanist, Erkenbrack, GoodDamon, Yahel Guhan, Casmith 789, Magiola-
ditis, Bongwarrior, VoABot II, Ling.Nut, Twsx, KConWiki, Adrian J. Hunter, DerHexer, Squidonius, MartinBot, NikNaks, Anaxial,
Kateshortforbob, CommonsDelinker, PrestonH, LedgendGamer, Djma12, Tgeairn, AlphaEta, J.delanoy, Nbauman, Boghog, Uncle Dick,
Kittyes, McSly, Mikael Häggström, Tarotcards, Omes, NewEnglandYankee, DadaNeem, Alnokta, Knoitall00, Anime101, Erick.Antezana,
Dorftrottel, SoCalSuperEagle, CardinalDan, Meiskam, DeathFlame131, Walik, TXiKiBoT, Oshwah, Vipinhari, CrashingWave, Anna
Lincoln, Leafyplant, Oskoreien, Earthdirt, Graymornings, Steve Smith, Twooars, AlleborgoBot, Caltas, Lameomclame, Flyer22 Reborn,
Yerpo, FAGGOODIKIKICOO, Techman224, Fratrep, OKBot, Mygerardromance, Denisarona, Brunhilda18, Naturespace, Forluvoft,
ClueBot, SantanuRoy, The Thing That Should Not Be, Wysprgr2005, Cptmurdok, Meekywiki, Drmies, Shinpah1, CounterVandalismBot,
Dylan620, Showman16, Arunsingh16, Mspraveen, Mumijary41, Foreveriamchangd, Royalmate1, Gundersen53, BOTarate, Thingg, Pen-
haligon 5, Horselover Frost, Conmiro, Versus22, Nona89, Johnuniq, Humanisticmystic, Avoided, Ilikepie2221, SilvonenBot, Itssodry, Ad-
dbot, Tcncv, Kastor48252, PlumCrumbleAndCustard, Vishnava, Ka Faraq Gatri, Download, Glane23, SpBot, LinkFA-Bot, West.andrew.g,
Shakiestone, Tide rolls, Lightbot, ‫زرشک‬, Loupeter, Quantumobserver, Ettrig, Legobot, Trannhatanh89, Luckas-bot, TheSuave, Yobot,
Fraggle81, Cflm001, II MusLiM HyBRiD II, AmeliorationBot, Maxí, IW.HG, Eric-Wester, Synchronism, Nutriveg, DemocraticLuntz,
Jim1138, 90, Materialscientist, OttoTheFish, The High Fin Sperm Whale, Citation bot, Eumolpo, Frankenpuppy, Carturo222, Xqbot, S h i
v a (Visnu), Sionus, Drilnoth, 6Sixx, - ), Astro Reeves, Jagbag2, RibotBOT, Crashdoom, Nikkirox69, Prapstylez, Srr712, LucienBOT, Jat-
las, Tobby72, Gouerouz, HJ Mitchell, A little insignificant, Cannolis, Fruit.Smoothie, Citation bot 1, Intelligentsium, Pinethicket, I dream
of horses, Robinhaw, Pokemaster50, A8UDI, Euphoria1611, Reconsider the static, Trappist the monk, Fox Wilson, Vrenator, 245684521,
Tbhotch, Reach Out to the Truth, MollyNYC, Onel5969, RjwilmsiBot, RamonyCajal, Gautamdey, Alison22, EmausBot, Lifelover6, Rheka,
Bub0297, RA0808, Brodyt66, Kwillis29, Wikipelli, K6ka, Margie2121, Darkfight, Anirudh Emani, Thecheesykid, Savh, JSquish, John
Cline, Susfele, Fæ, Alpha Quadrant (alt), Makecat, Wayne Slam, MacDaid, TyA, L Kensington, Donner60, Peter Karlsen, DASHB-
otAV, 28bot, Rocketrod1960, Petrb, ClueBot NG, Yambaram, Jack Greenmaven, Lchircus, Rtucker913, Snotbot, Histidine, Rezabot,
Widr, WikiPuppies, Newyorkadam, Helpful Pixie Bot, Waqarhafeez, Bibcode Bot, DBigXray, BG19bot, Jwchong, CatPath, PhnomPencil,
MusikAnimal, AvocatoBot, Bush6984, Amp71, Orangutans, Dan653, Mark Arsten, Merovigla, Joydeep, Olimpian1990, Fluffernutter2,
SciencePup, BattyBot, The Illusive Man, Fvandrog, Anne Stanford, EuroCarGT, Dexbot, Webclient101, Ptrw08, Lugia2453, Everything
Is Numbers, Frosty, Sfgiants1995, Hkfan2000, Kevin12xd, TheGiwiNinja, Melonkelon, Iztwoz, ProtossPylon, Kharkiv07, Ginsuloft, Tri-
olysat, Gyana.srivastava, Sahil Jain04, Jlmalcos, Mjt3727, AlmaMer, Anon685, Orly.alter, Monkbot, Shazzymc25, Raytuzio, 115ash,
Dumb lag, Ternary.pulsar, Evil.orange.peel, Hgcdplayrz23, KasparBot, Sweepy, Jschmidt3112, Kriti kamboj, Gaelan, Alexcalderon72728
and Anonymous: 762

9.2 Images
• File:Animal_cell_cycle-en.svg Source: https://upload.wikimedia.org/wikipedia/commons/2/2f/Animal_cell_cycle-en.svg License: CC0
Contributors: Own work Original artist: Kelvinsong
• File:Cell_Cycle_2-2.svg Source: https://upload.wikimedia.org/wikipedia/commons/e/e0/Cell_Cycle_2-2.svg License: CC-BY-SA-3.0
Contributors:
• Cell_Cycle_2.svg Original artist: Cell_Cycle_2.svg: *Cell_Cycle_2.png: Original uploader was Zephyris at en.wikipedia
• File:Commons-logo.svg Source: https://upload.wikimedia.org/wikipedia/en/4/4a/Commons-logo.svg License: ? Contributors: ? Original
artist: ?
• File:Paul_Nurse_portrait.jpg Source: https://upload.wikimedia.org/wikipedia/commons/a/ac/Paul_Nurse_portrait.jpg License: CC
BY-SA 3.0 Contributors: OTRS submission by Ryoko Mandeville on behalf of Paul Nurse Original artist: Not specified in the OTRS
submission
• File:Plant_cell_cycle.svg Source: https://upload.wikimedia.org/wikipedia/commons/f/f0/Plant_cell_cycle.svg License: CC BY-SA 3.0
Contributors: Own work Original artist: Kelvinsong
• File:Question_book-new.svg Source: https://upload.wikimedia.org/wikipedia/en/9/99/Question_book-new.svg License: Cc-by-sa-3.0
Contributors:
Created from scratch in Adobe Illustrator. Based on Image:Question book.png created by User:Equazcion Original artist:
Tkgd2007
• File:Signal_transduction_pathways.svg Source: https://upload.wikimedia.org/wikipedia/commons/b/b0/Signal_transduction_
pathways.svg License: CC BY-SA 3.0 Contributors: http://en.wikipedia.org/wiki/File:Signal_transduction_v1.png Original artist:
cybertory
9.3 Content license 9

• File:TPI1_structure.png Source: https://upload.wikimedia.org/wikipedia/commons/1/1c/TPI1_structure.png License: Public do-

main Contributors: based on 1wyi (http://www.pdb.org/pdb/explore/explore.do?structureId=1WYI), made in pymol Original
artist: →<ₐ ᵣₑ ₌'// ₒ ₒ . ᵢ ᵢ ₑ ᵢₐ.ₒᵣ / ᵢ ᵢ/U ₑᵣ:A ₐTₒ ' ᵢ ₑ₌'U ₑᵣ:A ₐTₒ '>A ₐ</ₐ><ₐ ᵣₑ ₌'// ₒ ₒ . ᵢ ᵢ ₑ ᵢₐ.ₒᵣ / ᵢ ᵢ/U ₑᵣ_ ₐ :A ₐTₒ ' ᵢ ₑ₌'U ₑᵣ ₐ :
A ₐTₒ '>Tₒ </ₐ>
• File:Wilson1900Fig2.jpg Source: https://upload.wikimedia.org/wikipedia/commons/3/37/Wilson1900Fig2.jpg License: Public domain
Contributors: Figure 2 of: Wilson, Edmund B. (1900) The cell in Development and Inheritance (2nd ed.), New York City: The Macmillan
Company Original artist: Edmund Beecher Wilson

9.3 Content license

• Creative Commons Attribution-Share Alike 3.0