How It Works - UK (2020-02)

HEALTH

‘Doughnut-shaped’ DNA makes

cancer more aggressive

WordsbyYaseminSaplakoglu

C

ancercellsmayowesomeoftheir

destructivenaturetounique,‘doughnut-

shaped’DNA,accordingtoa recent

study.PublishedinthejournalNature, thestudy

foundthatinsomecancercells,DNAdoesn’t

packintothread-likestructureslikeit doesin

healthycells– rather,thegeneticmaterialfolds

intoa ring-likeshapethatmakesthecancer

moreaggressive.

“DNAconveysinformationnotonlyinits

sequence,butalsoinitsshape,”saidco-senior

authorPaulMischel,a professorofpatholog yat

theUniversit yofCaliforniaatSanDiego.Asyou

mayrememberfrombiolog yclass,mostofour

DNAispackedtightlyinsidecells'nucleiin

structuresknow naschromosomes.

Thisjam-packedstructureallowsforsome

genestobeaccessiblebythemoleculesthat

‘read’andcarr youtthegeneticinstructions,

whileothergenesstayhidden.Whatresultsis

highlyregulatedmachiner ythatkeepsthecell

fromcarr y ingoutunwantedgenetic

instructionsandfromreplicating– creatingnew

‘daughtercells’– inanerraticway.

“Ever y thingwe’velearnedaboutgeneticssays

thatchanges[incells]shouldbeslow,”Mischel

toldLiveScience. Butyearsago,Mischelandhis

teamfoundthatina certaint y peofbrain

cancercalledglioblastoma,

DNAcontainsalltheinformation

thatanorganismneedstofunction

http://www.howitworksdaily.com How It Works 013

tumours “seemed to be able to change at a rate

that just didn’t make any sense.” The tumour

cells, as they div ided into daughter cells, seemed

to be somehow amplif y ing the expression of

oncogenes – genes that can transform a regular

cell into a cancerous one.

It turned out that some of these amplified

copies of oncogenes had “untethered themselves

from chromosomes,” Mischel said. Hav ing

broken loose from the chromosomes, they

were hanging out on other pieces of DNA

inside the cell. They then found that these

‘extrachromosomal’ pieces of DNA – ecDNA –

actually occur in nearly half of human cancers

but have rarely been detected in healthy cells.

In this recent study, they figured out why

ecDNA is so robust. A combination of imaging

and molecular analysis revealed that these

pieces of DNA are w rapped around proteins in a

ring shape, similar to the circular DNA found in

bacteria. This ring shape makes it much easier

for the cell’s machiner y to access a slew of

genetic information – including the oncogenes

• so that it can quickly transcribe and express
  them, for example, instruct a healthy cell to turn
  cancerous, Mischel said. This easy accessibility
  allows tumour cells to generate large amounts of
  tumour-promoting oncogenes, evolve quickly
  and adapt easily to a changing env ironment.

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