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Lyrical DNA

Round Again

Cell CommunicationLyrical DNASongs

A song about the eukaryotic cell cycle. The lyrics run from a cell growing in G1, checking itself before copying its DNA or stepping aside into G0, through the proteins that drive its key transitions, DNA replication into sister chromatids and the preparations of G2, to the chromosome movements of mitosis, the two identical nuclei they produce, and cytokinesis turning one cell into two. Select any highlighted line to see the biology behind it.

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Interactive lyrics

Lines with a dotted underline and a + marker have an explanation. Select one and the science appears beside the lyrics. Everything else is ordinary lyric text.

Intro

I wake up with the list to do,

Build a little more, then make it two.

Woo!

Verse 1

Pre-Chorus

Phase by phase, I know the road,

Build the parts and share the code.

Chorus

Round again, round again,

Round again, round again,

I have got a cycle and a way to begin.

Grow it, copy it, ready, go,

Round again, or rest in G0.

Verse 2

I am building up the energy to split this life in five

Break

No, not five.

Two.

Pre-Chorus

Phase by phase, I know the road,

Build the parts and share the code.

Chorus

Round again, round again,

G1 to S, then G2 and then

Mitosis turns one story into two,

Cytokinesis carries the whole thing through.

Round again, round again,

I have got a cycle and a way to begin.

Grow it, copy it, ready, go,

Round again, or rest in G0.

Bridge

Final Chorus

Round again, round again,

G1 to S, then G2 and then

Mitosis shares the duplicated view,

Cytokinesis makes the one cell two.

Round again, round again,

Some leave the road, some reenter it again.

Grow it, copy it, ready, go,

Round again, or rest in G0.

Outro

Phase by phase,

Round again.

Round again.

Concepts covered

G1 growth and organelle duplicationG1 is the cell at work. It carries out its normal metabolic jobs while it grows, making new proteins, membranes and cytosol so it can get bigger. It also increases its stock of organelles. Mitochondria and, in plants, chloroplasts multiply by splitting in two, while membrane systems such as the endoplasmic reticulum expand from existing membrane. The aim is a cell large and well stocked enough that, once it divides, each daughter starts out with a working set of parts.
The G1 checkpointA checkpoint late in G1, before replication, weighs whether the cell is big enough, has enough nutrients, has signals to divide and has undamaged DNA. If a test fails, the cell halts: it waits, repairs the damage or leaves for G0, and DNA beyond repair may trigger apoptosis. Later checkpoints confirm in G2 that replication is complete and, in mitosis, that every chromosome is attached to the spindle. Mutations that disable these checks let damaged cells keep dividing, a step toward cancer.
G0, the nondividing stateA cell in G0 has stopped dividing but keeps working. One that steps out of the cycle, usually from G1, can be fully functional, and many of the body's cells spend their working lives in G0. Some specialized cells, such as most mature nerve cells, stay there long term. Others keep the option to return. Liver cells, for instance, normally sit in G0 but can reenter G1 when signals released after injury reach them, and they divide until the liver's original mass is restored, then return to G0.
Cyclin-CDK control of phase transitionsWhat pushes a cell from G1 into S, and from G2 into mitosis, is a set of regulatory proteins. Cyclin-dependent kinases, or CDKs, are present throughout the cycle but inactive until a cyclin binds them. Cyclin levels rise and fall at set points in each cycle, hence the name. An active cyclin-CDK complex adds phosphate groups to target proteins, switching on the events of the next phase. Breaking down the cyclin then shuts the complex off, so the cycle moves forward instead of slipping back.
Two genetically identical nucleiMitosis hands each of two new nuclei one sister chromatid of every replicated chromosome. Both therefore receive the complete genome, the same DNA sequences the parent cell carried, and apart from rare copying errors they are genetically identical. That fidelity is why mitosis can build a growing body, repair damaged tissue and carry out asexual reproduction. It is not meiosis: it does not halve the chromosome number.
Cytokinesis: cleavage furrow or cell plateCytokinesis divides what mitosis leaves whole: the cytoplasm, its organelles and the plasma membrane, shared between two daughter cells. It usually begins as mitosis ends. In animal cells a ring of protein filaments just under the membrane tightens around the middle, forming a cleavage furrow that pinches the cell in two. A plant cell's rigid wall cannot pinch, so vesicles gather at the midline and fuse into a cell plate that grows outward and becomes the new wall between the daughters.
DNA replication in S phaseS stands for synthesis, the phase in which the cell copies its entire genome. The DNA is still loosely packed as chromatin, and replication starts at many points along each chromosome, which lets very long molecules be copied in a manageable time. The two strands of each double helix are unwound and separated, and each serves as the template for a new partner strand, so every copy keeps one original strand. Controls ensure each stretch is copied once and only once per cycle.
Sister chromatids and the centromereEach replicated chromosome consists of two sister chromatids, identical DNA copies held together at a region called the centromere. The pairing is between identical copies, unlike homologous chromosomes, which come one from each parent and can carry different versions of the same genes. The two chromatids still count as a single chromosome. They stay attached until anaphase, when the connection is released and each chromatid becomes an independent chromosome.
G2 preparation for divisionG2 is spent getting ready to divide. Protein synthesis supplies proteins that mitosis will rely on, such as tubulin for the spindle's microtubules. ATP is produced in large quantities too, and division draws on it: motor proteins that help build the spindle and move chromosomes run on ATP, and so does the contraction that later divides an animal cell's cytoplasm. What the cell readies for the busy times is its rate of production, so that supply keeps pace with the work of dividing.
Centrosomes and spindle polesA centrosome is the main microtubule organizing center of an animal cell, a small body near the nucleus built around a pair of centrioles. It is copied once per cycle, and by the end of G2 the cell holds two. Those two are the final tools: in prophase they move to opposite sides of the cell, and the microtubules growing from them form the mitotic spindle, with one centrosome at each pole. Most plant cells have no centrosomes and assemble a spindle without them.
Time spent in interphaseInterphase, the run of G1, S and G2 in that order, takes most of a typical cycle's time, and mitosis is brief by comparison. A slide of a fast-growing root tip shows it: most cells are in interphase and few are dividing. Because each cycling cell was caught at a random point in its cycle, the share found in each stage roughly reflects how long that stage lasts. How long a full cycle takes varies widely between cell types, and most of that difference comes from how long G1 lasts.
Chromosome movement in mitosisFour steps carry the chromosomes through mitosis. In prophase the sister chromatids condense into compact, visible chromosomes and the spindle begins to form. In metaphase spindle fibers line the chromosomes up along the cell's equator. In anaphase the sisters separate and are pulled toward opposite poles. In telophase the spindle breaks down and a nuclear envelope forms around each set. Compaction makes the move safe, since long, loose DNA would tangle and break if dragged across the cell.

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