Proteins readying chromosomes for mitosis identified

Scientists have solved a longstanding puzzle of how cells are able to tightly package DNA to enable healthy cell division.

Their findings shed light on how single cells can compact DNA 10,000-fold to partition it between two identical cells - a process that is essential for growth, repair and maintenance in living beings.

Until now, the details were not clearly understood, but biochemical and imaging technologies combined with sophisticated mathematical analysis have revealed these for the first time.

They show the processes that enable copies of DNA in an existing cell to take on the necessary structure to divide correctly in two new cells.

The study clarifies one key aspect of how cells are able to constantly divide and renew, which has challenged scientists since the late 19th century.

Its findings will enable much more detailed research into the cell division process which, when it goes faulty, can lead to cancer, congenital disease and other conditions.

Researchers found that when cells divide, strands of genetic material are folded to form a series of compacted loops. These loops project out from a helix-shaped axis, like steps on a spiral staircase.

A key set of proteins known as condensin II controls the formation of these large loops of DNA and anchors them to the central spiral axis.

A related protein group, condensin I, acts to pinch smaller loops within these larger coils, enabling the genetic material to be compacted efficiently in preparation for cell division.

The combination of a helical axis, projecting loops of DNA and dense packing compacts the genome into orderly structures that can be accurately split when cells divide.

Authors show that the interphase organization is rapidly lost in a condensin-dependent manner and arrays of consecutive 60 kb loops are formed. During prometaphase ~80 kb inner loops are nested within ~400 kb outer loops.

The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral-staircase condensin scaffold. The size of helical turns progressively increases during prometaphase to ~12 Mb.

Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins while condensin II is required for helical winding.

The study pinpoints the role of condensin I and condensin II, so-called molecular machines, which were previously known to have a key association with cell division.

The study is published in the journal Science.

https://www.ed.ac.uk/news/2018/dna-study-casts-light-on-cell-division-mystery