JAN 30, 2018 5:03 PM PST

Packaging the Genome

WRITTEN BY: Carmen Leitch

High powered microscopy has been enabling researchers to get a look at some of life’s most basic processes. Now, scientists have constructed simulations of chromosomes being packaged into condensed structures, which happens just before cells divide. The work, by Howard Hughes Medical Investigators, has been reported in Science.

“This is the most fundamental process of genetics,” said study coauthor and Howard Hughes Medical Institute (HHMI) Investigator Job Dekker. Chromosomes can break when genomic packing goes awry, and it's  a hallmark of cancer.

Scientists first observed chromosomes under a microscope over a century ago, and Dekker noted that this work solves a mystery going back that far. Chromosomes exist as tangled masses in the nucleus; Dekker likened them to little blobs. When cells prepare to divide into daughter cells, chromosomes coil up, jamming about six feet of DNA into microscopic packages. After being sent to the daughter cells, the chromosomes can relax again.

Investigators have long known how chromosomes were structured, and several years ago, Dekker and colleagues found that tightly packed chromosomes were arrayed as consecutive loops. The transition between those states and the speed with which it occurs was a question. “The whole process happens in 10 to 15 minutes,” said Dekker. “It’s unbelievable.” The finding was controversial; some researchers thought chromosome are twisted into helices. 

Dekker, and a team that included William Earnshaw of the University of Edinburgh’s Wellcome Trust Centre for Cell Biology and Leonid Mirny of the Massachusetts Institute of Technology synchronized chicken cells; all of them started packing chromosomes simultaneously. Then they took snapshots of the chromosomes at various time points.

The team fixed the chromosomes in place and looked at the DNA sequence where strands touched. That revealed clues about the architecture, which the team combined with computer simulations. The researchers were then able to predict how chromosomes make the change from a blob to a rod. “Because the structures are so totally different, you think, ‘Oh my, that must be a highly complicated and difficult process,’” Dekker said.

The packing strategy is efficient, which may show how cells can repeat the process over and over, Dekker noted. Chromosomes get pushed through small protein motors, ring-like structures called condensins, to form loops. Condensin II then weaves them into wide loops, while condensin I splits big loops into small ones. Hundreds of these loops then get twisted into spirals.

The new work also unifies what seemed to be conflicting views of mitotic chromosomes. They can be arranged in loops, but they can be helical as well, Dekker said. “I find this extremely satisfying,” he said. “I always aim for consilience. If you’re confronted with datasets that supposedly tell you two different things, can you find a way for them both to be right?”

 

Sources: HHMI

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 19, 2020
Cancer
Using qPCR to Diagnose Common Cancer Mutations in Lung Cancer
OCT 19, 2020
Using qPCR to Diagnose Common Cancer Mutations in Lung Cancer
Cancer is a disease characterized by DNA mutations. These mutations, while sometimes small, can cause havoc in a cell&rs ...
OCT 19, 2020
Genetics & Genomics
Early Childhood Trauma Affects Metabolism in the Next Generation
OCT 19, 2020
Early Childhood Trauma Affects Metabolism in the Next Generation
Traumatic experiences can have a lasting impact, and kids that suffer through them can feel the effects for a lifetime. ...
OCT 27, 2020
Immunology
The Genetics of Skin Inflammation, Seen With Unprecedented Clarity
OCT 27, 2020
The Genetics of Skin Inflammation, Seen With Unprecedented Clarity
A recent study published in Immunity details MIT scientists’ exploration of the underlying mechanisms of inflammat ...
OCT 26, 2020
Genetics & Genomics
Does a 'Mismatch' Between Diet and Biology Cause Poor Health?
OCT 26, 2020
Does a 'Mismatch' Between Diet and Biology Cause Poor Health?
People that eat a 'paleo' diet operate under the idea that we should be eating more like our ancestors, and that metabol ...
NOV 19, 2020
Cell & Molecular Biology
A Different View of Chromosomes
NOV 19, 2020
A Different View of Chromosomes
Many of us are familiar with typical diagrams of a chromosome, which is usually drawn like a stubby X. While that pictur ...
NOV 23, 2020
Microbiology
Drug Resistance in Tuberculosis Involves a Unique Mechanism
NOV 23, 2020
Drug Resistance in Tuberculosis Involves a Unique Mechanism
The pathogenic bacterium that causes tuberculosis, Mycobacterium tuberculosis, does not multiply quickly, so researchers ...
Loading Comments...