Dynamics of DNA replication revealed at the nanoscale

June 25, 2020

DNA replication is a process of critical importance to the cell, and must be coordinated precisely to ensure that genomic information is duplicated once and only once during each cell cycle. Using super-resolution technology a University of Technology Sydney led team has directly visualised the process of DNA replication in single human cells.

This is the first quantitative characterization to date of the spatio-temporal organisation, morphology, and in situ epigenetic signatures of individual replication foci (RFi) in single human cells at the nanoscale.

The results of the study, published in PNAS (Proceedings of the National Academy of Sciences) give new insight into a poorly understood area of DNA replication namely how replication origin sites are chosen from thousands of possible sites.

Lead author of the study, biophysicist Dr Peter Su from UTS Institute of Biomedical Materials and Devices (IBMD), explains that it's known DNA replication is initiated at numerous sites along the chromosomes.

"These are known as replication origins, which are clustered into thousands of replication domains (RDs) across the genome, which in turn cluster within the cell nucleus as RFi " he says.

"Such organization is critically important for the cell but how replication origins are chosen within individual RDs remains poorly understood, and it is unclear whether the origins are activated randomly or preferentially near certain chromatin features," he says. Chromatin helps package DNA material together so it can fit efficiently within the nucleus of a cell a, thus protecting the DNA from damage.

The collaboration with scientists from Peking University and National University of Singapore revealed a distinct pattern of replication propagation dynamics that reverses directionality across S-phase of the cell cycle, and is diminished upon knockdown of CTCF, a key regulator of 3D genome architecture.

The researchers say that together with simulation and bioinformatic analyses, these findings point to a model in which replication is preferentially activated on CTCF-organized looped chromatin structures, and suggest a non-random selection mechanism for replication activation at the sub-RD level.

Dr. Su said: "Our findings shed critical insights into the role local epigenetic environment plays in coordinating DNA replication across the genome, and could have wide-ranging implications for our understanding of how multi-scale chromatin architecture controls the organization and dynamics of diverse intranuclear processes in space and time."

University of Technology Sydney

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.