Nav: Home

Microbiology: Many forks make light work

June 07, 2017

New insights into the control of DNA replication and cell division in Corynebacterium glutamicum, a biotechnologically important microorganism, could help to optimize the industrial production of amino acids.

The rod-shaped Gram-positive soil bacterium Corynebacterium glutamicum plays an important role in biotechnology. As its species name indicates, C. glutamicum synthesizes glutamic acid (one of the 20 canonical amino acids found in proteins) in large quantities, and is used for large-scale production of this and many other amino acids. However, yields are constrained by the fact that, in comparison with bacteria like Escherichia coli, corynebacterial cultures grow relatively slowly. Microbiologist Professor Marc Bramkamp from Ludwig-Maximilians-Universitaet (LMU) in Munich and his research team have now taken a closer look at C. glutamicum's mode of growth and proliferation, and uncovered previously unknown aspects of these processes, which can be exploited to enhance its growth rate.

Bacterial cell division is preceded by the replication of the bacterial chromosome(s). Replication begins from a single origin, and entails the segmental dissociation of the two strands of the DNA's double helix. Localized separation of the DNA strands takes place at what is known as a replication fork. Each strand then acts as a template for the enzymatic synthesis of the complementary strand. The whole process thus leads to the production of two copies of each parental chromosome, which are distributed equally between the two daughter cells. In many bacterial species, including E. coli (which has only one, circular chromosome), generation times are actually shorter than the time taken to fully replicate the chromosome. Microorganisms accomplish this feat by initiating a second round of DNA replication prior to the termination of the preceding one. As a result, daughter cells contain chromosomes with already ongoing new rounds of replication at the time of cell division. This mode of cell proliferation is termed 'multifork' replication, because each replicating molecule will contain several replication forks.

It had been thought that corynebacterial growth rates are sufficiently slow to ensure that its chromosomes have ample time to replicate fully before cell division occurs - and therefore that members of this genus do not make use of multifork replication. The LMU researchers observed growing C. glutamicum cells over the course of many generations, with the aid of high-resolution microscopy. Much to their surprise, they found that the species is in fact capable of implementing the multifork mode of DNA replication. "This is a significant discovery, because it implies that it should in principle be possible to enhance the growth rate of C. glutamicum," Bramkamp says. "At all events, its rate of DNA replication is not a limiting factor."

In addition, the new study shows that C. glutamicum cells normally harbor two complete sets of chromosomes (and are therefore 'diploid'), while the vast majority of bacterial species are thought to contain only one. The diploid condition confers a number of advantages. For example, it facilitates healing of double-stranded DNA breaks and other types of DNA damage, because the unaffected copy of the chromosome can serve as a template for the repair process. This is of particular significance to bacteria that are exposed to potentially DNA-damaging influences such as UV light. The authors of the new study therefore assume that the diploid character of C. glutamicum represents an adaptation to high levels of environmental stress.

C. glutamicum is also closely related to a number of clinically significant pathogens, including the species responsible for infectious diseases such as diphtheria, tuberculosis or leprosy. "Since fundamental cell biological processes in closely related organisms are very often similarly structured, our findings should allow us to make reliable predictions in relation to the growth modes of these pathogens," Bramkamp points out. He and his colleagues believe that their results will also facilitate efforts to develop new treatments for corynebacterial infections, based on the inhibition of DNA replication.

Ludwig-Maximilians-Universität München

Related Dna Articles:

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.
In one direction or the other: That is how DNA is unwound
DNA is like a book, it needs to be opened to be read.
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.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
More Dna News and Dna Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab