Cells access data from genetic cotton reels

Australian geneticists have unravelled part of the mystery about how nature can usefully access genetic information in cells despite it being so tightly packed away.

The discovery, they say, helps solve what is effectively an input/output problem caused by the need for cells to pack metres of DNA into a space just millionths of a metre across while at the same time reading, copying and repairing the information held in the DNA. 

It also helps provide pathways to understand how defects in this process contribute to diseases such as schizophrenia and cancer.

Writing in the journal Nature Communications, a team led by Joel Mackay from the University of Sydney reveals that a particular motor protein, CHD4, is used to access genetic information tightly spooled onto what can be imagined as “genetic cotton reels”.

“This protein effectively remodels our DNA to allow access to the information that determines the fate of a cell and its ability to respond to signals from the outside,” Mackay says. 

“It is a critical protein for almost all the work that cells do, including cell division and DNA repair.”

Mackay adds that understanding this process is critical for developing treatments for neurodevelopmental disorders and some cancers.

“These illnesses are in part triggered by defects in the remodelling of the DNA that is driven by this process,” he says.

“The protein CHD4 and its close partners are emerging as important risk factors in polygenic neurodevelopmental disorders, schizophrenia and bipolar disorder, as well as in rare monogenic disorders, such as GAND, which causes severe mental disability.”

Mutations in the CHD4 protein that impair its function are also associated with endometrial carcinoma.