Watching single strands of DNA being prepped for repair may help researchers understand the origins of breast cancer.
In a new study, graduate student Jason Bell imaged individual strands of bacterial DNA as they were coated with a protein called RecA. Studying how this process works gives insights into the "mediator" proteins responsible that facilitate it. In humans, one of those mediators is the protein BRCA2, which is strongly associated with breast cancer. RecA, called Rad51 in humans, helps the single strand of DNA find its complementary, matching strand elsewhere in the chromosome. The RecA protein has to displace another protein, imaginatively named single-strand DNA-binding protein, to get to the DNA.
The researchers were able to watch in real time as the RecA units displaced single-strand DNA-binding proteins and then spread in both directions until the whole strand was covered. They found that the process has to start with two molecules of RecA attaching to the DNA. Then single molecules of RecA can be added at either end, similar to adding beads on a string.
Proteins assembling on single-strand DNA . Videography by Jason Bell and Steve Kowalczykowski
"It's clear that in cells, DNA breaks all the time, and there's machinery to repair those breaks and retain genetic integrity," said Stephen Kowalczykowski, distinguished professor of microbiology at UC Davis and senior author of the paper. To repair a break in the DNA double helix, a single strand has to seek out and find its matching sequence on the opposite strand -- a task that Kowalczykowski compares to finding a needle in a haystack. To do that, the single strand first has to be coated with a protein called RecA. "The RecA/DNA filament is the machine that looks for that needle," he said.
One surprise was that in the absence of mediators, the process was relatively slow, Kowalczykowski said. It took about 30 minutes to coat a strand -- longer than the time E. coli takes to go through a cell division cycle.
The mediator proteins are crucial for controlling the speed at which RecA assembles on the single strand of DNA, Kowalczykowski said. Too slow, and DNA breaks would not be repaired properly; too fast, and it would capture and coat the short pieces of single-stranded DNA briefly produced during normal DNA replication. Instead, the process only works on DNA that persists because it is actually damaged or broken.
"I'm sure that BRCA2 works in the same way," he said.
Published in Nature. Co-authors are postdoctoral researchers Jody Plank and Christopher Dombrowski.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- Some Celiac Disease May Be Due To Viruses
- How A Former Naturopath Can Help Unravel The Trickery of Alternative Medicine
- Out Of Africa: What They Do Not Tell Us
- Pubic Hair Grooming Common Among Some US Women
- Brain Cancer: Why Glioblastoma Is So Difficult To Treat
- Little To No Association Between Butter Consumption And Chronic Disease Or Total Mortality
- Thinking 'I Can Do Better' Really Can Improve Performance, Study Finds
- "Thank you for your support - but since the comment you refer to was advocating the shutting down..."
- "Instead of ND, substitute DD, and you have a whole other basket of charlatans - and that comment..."
- " Some parts from my second response to Nina Teicholz article ( http://www.bmj.com/content/351/bmj..."
- "Science researchers did the CARET study, to see if vitamin A could chemo-prevent lung cancer (it..."
- "Whether or not a conclusion can be used for bad purposes should never be the reason to shut down..."
- Study finds that plant growth responses to high carbon dioxide depend on symbiotic fungi
- Telomere length is indicator of blood count recovery in treatment of Acute Myeloid Leukemia
- Natural metabolite can suppress inflammation
- New technology helps ID aggressive early breast cancer
- US needs greater preparation for next severe public health threats, panel finds