Accurate transmission of genetic information requires the precise replication of DNA. Errors in DNA replication are common and nature has developed several cellular mechanisms for repairing these mistakes. Mutations, which can be deleterious (development of cancerous cells), or beneficial (evolutionary adaption), arise from uncorrected errors. When one or many cells repair themselves using the efficient BIR method, accuracy is lost.
"When BIR occurs, instead of using a "band aid" to repair a chromosomal break, the broken piece invades another chromosome and initiates replication which happens at the wrong place and at the wrong time and probably with participation of wrong proteins," said Anna Malkova, Ph.D., associate professor of biology at the School of Science at IUPUI, who led the study.
The researchers used yeast to investigate the level of mutagenesis associated with BIR and found that the method's proclivity to cause mutation was not affected by where on the DNA the repair was made.
Why is BIR so inaccurate as compared to normal replication?
"We didn't find a smoking gun," said Malkova, also an adjunct associate professor of medical and molecular genetics at the Indiana University School of Medicine. "We think there are at least four changes to replication machinery that must occur to create a perfect storm or synergy which make BIR repair so mutagenic."
For example, during BIR, the researchers found a dramatic increase in concentration of nucleotides -- the building blocks used to form DNA.
"Our findings strongly suggest that mutagenesis caused by BIR doesn't happen slowly, it occurs in surges – sudden bursts which may lead to cancer," said Malkova, who is a geneticist. "We plan to continue investigating BIR in the hope of finding clues as to why this mechanism of cell repair is so likely to cause mutations. The ultimate goal, of course, is to prevent those mutations that cause cancer."
Co-authors of the study, "Break-induced Replication Is Highly Inaccurate" are Angela Deem, Tiffany Blackgrove, Alexandra Vayl, Barbara Coffey, and Ruchi Mathur of the School of Science at IUPUI and Andrea Keszthelyi and Andrei Chabes of Umea° University. The work was supported by the National Institutes of Health (U.S), the Swedish Foundation for Strategic Research; the Swedish Research Council, and the Swedish Cancer Society.
The School of Science at IUPUI is committed to excellence in teaching, research and service in the biological, physical, behavioral and mathematical sciences. The School is dedicated to being a leading resource for interdisciplinary research and science education in support of Indiana's effort to expand and diversify its economy. For more information, visit www.science.iupui.edu
Cindy Fox Aisen | EurekAlert!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences