Unraveling the genome in 3D-space

Date:
September 23, 2020
Source:
IMBA- Institute of Molecular Biotechnology of the Austrian Academy
of Sciences
Summary:
Proper folding of extremely long chromosomal DNA molecules is
crucial for the correct functioning of the cell. Scientists
developed a groundbreaking method to map contact points between
replicated DNA molecules, thereby elucidating how the genome is
folded inside the nucleus of human cells.



FULL STORY ==========================================================================
The cells that make up our body are tiny, each of them measuring only micrometers in diameter. The ensemble of chromosomal DNA molecules that
encode the genome, on the other hand, measures almost 2 meters. In order
to fit into cells, chromosomal DNA is folded many times. But the DNA
is not merely squeezed into the nucleus in a random manor but folded
in a specific and highly regulated structure. The spatial organization
of chromosomal DNA enables regulated topological interactions between
distant parts, thereby supporting proper expression, maintenance, and
transport of the genome across cell generations.


========================================================================== Breaks in our DNA, which can occur spontaneously or result from
irradiation or chemical insults, can lead to severe problems since they
foster mutations and can ultimately lead to cancer. But not every DNA
break has disastrous consequences, since our cells have ingenious ways of repairing the damage. One of the main DNA repair pathways involves copying
the missing information on the damaged DNA from the replicated sister chromatid. For this to occur, the two DNA molecules of sister chromatids
need to come close together at the exact same genomic position. How the
two DNA molecules are organized relative to each other to support this important repair pathway, however, has remained unclear.

The team around Daniel Gerlich developed a method that solves this
problem.

"Current methods to map the folding of DNA have a serious blind spot:
They are not able to distinguish identical copies of DNA molecules. Our approach to solve this was to label DNA copies in a way such that
we can discriminate them by DNA sequencing" explains Michael Mitter,
doctoral student in Dr. Gerlich's lab and first author of the current publication in Nature. Using this approach, the researchers were able to
create the first high resolution map of contact points between replicated chromosomes.

"With this new method, we can now study the molecular machinery regulating
the conformation of sister chromatids, which will provide insights into
the mechanics underlying the repair of DNA breaks and the formation of rod-shaped chromosomes in dividing cells, which is required for proper transport the genome to cell progeny," says Daniel Gerlich about the
project, which is financed by the Vienna Science and Technology Fund
(WWTF) and was a fruitful collaboration of several research groups at the Vienna BioCenter, including the Ameres and Goloborodko labs at IMBA, and
the Peters lab at the neighboring Institute of Molecular Pathology (IMP).


========================================================================== Story Source: Materials provided by IMBA-_Institute_of_Molecular_Biotechnology_of_the
Austrian_Academy_of_Sciences. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Michael Mitter, Catherina Gasser, Zsuzsanna Takacs, Christoph C. H.

Langer, Wen Tang, Gregor Jessberger, Charlie T. Beales, Eva
Neuner, Stefan L. Ameres, Jan-Michael Peters, Anton Goloborodko,
Ronald Micura, Daniel W. Gerlich. Conformation of sister
chromatids in the replicated human genome. Nature, 2020; DOI:
10.1038/s41586-020-2744-4 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200923124653.htm

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