Mathematical analysis helps untangle bacterial chromosomes

November 11, 2013

SAN FRANCISCO, Nov. 11, 2013 -- When an E. coli cell divides, it must replicate its circular chromosome and pull the resulting circles apart to take up residence in two new cells. It sounds easy enough -- like a magician's trick with rings -- but actually involves a complicated process of unknotting and unlinking of tangled DNA.

In a new study, published online this week in the journal Proceedings of the National Academy of Sciences, SF State Associate Professor of Mathematics Mariel Vazquez and an international team of scientists offer a mathematical analysis of how these chromosomal rings are unlinked by XerCD recombination enzymes.

Antibiotics like ciprofloxacin, prescribed for E. coli infections, target topoisomerases, another type of enzyme involved in DNA unlinking. When treated with these drugs, bacterial cells may find other modes of unlinking like the one presented in Vazquez' study, thus giving the cells a chance for survival. Understanding this unlinking process in E. coli, Vazquez noted, "could also lead to the design of better antibacterial drugs, with a clear positive effect on human health."

Infections by pathogenic E. coli and other bacteria pose a high risk to human health. According to the Centers for Disease Control and Prevention, each year in the United States at least 2 million people become infected with bacteria that are resistant to antibiotics. At least 23,000 people die each year as a direct result of these infections. In order to understand bacterial infections, it is essential to study how cells such as E. coli divide.

Biological experiments had given Vazquez and her colleagues some clues as to how the interlinked E. coli chromosomes separate prior to cell division. But the experiments could not provide a clear picture of the steps along the way to separation.

To fill in this picture, the researchers proposed a rigorous mathematical analysis that used the tangle method to model the changes that take place during the separation. In this case, the "tangle" represents two specific sites along the chromosome bound together by the recombination enzymes. They confirmed that the separation takes place in a stepwise fashion. Chromosomes interlinked after replication are converted into knots, then links again, then knots, until two free circles remain.

The researchers mention that further biological experiments can help justify the assumptions in the mathematical model, but acknowledge that those experiments would be extremely challenging to carry out. "In their absence, the mathematical analysis makes a clear-cut advance over previous biological studies," Vazquez said.

Vazquez stressed that mathematics, physics, computer science and statistics all have a role to play alongside biology in understanding DNA topology.

"It is important for people to know that DNA is not just a sequence of letters. It is a very long molecule that can adopt a complex three-dimensional structure when packaged inside a cell nucleus," she said. "Every biological process that involves DNA will be affected by its topology, and topological changes can have important biological implications."

In 2011, Vazquez was awarded a National Science Foundation CAREER grant to carry out DNA topology studies. As part of the grant, Vazquez works with local elementary schools in the San Francisco Math Circles program. In 2012, she received the Presidential Early Career Award for Scientists and Engineers (PECASE) for her work.
The study "FtsK-dependent XerCD-dif recombination unlinks replication catenanes in a stepwise manner," was published in the November 11 2013 issue of the journal Proceedings of the National Academy of Sciences.

SF State is the only master's-level public university serving the counties of San Francisco, San Mateo and Marin. The University enrolls nearly 30,000 students each year and offers nationally acclaimed programs in a range of fields -- from creative writing, cinema and biology to history, broadcast and electronic communication arts, theatre arts and ethnic studies. The University's more than 219,000 graduates have contributed to the economic, cultural and civic fabric of San Francisco and beyond.

San Francisco State University

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 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