Faced with a threat, the brain has to act fast, its neurons making new connections to learn what might spell the difference between life and death. But in its response, the brain also raises the stakes: As an unsettling recent discovery shows, to express learning and memory genes more quickly, brain cells snap their DNA into pieces at many key points, and then rebuild their fractured genome later.
The finding doesn’t just provide insights into the nature of the brain’s plasticity. It also demonstrates that DNA breakage may be a routine and important part of normal cellular processes—which has implications for how scientists think about aging and disease, and how they approach genomic events they’ve typically written off as merely bad luck.
The discovery is all the more surprising because DNA double-strand breaks, in which both rails of the helical ladder get cut at the same position along the genome, are a particularly dangerous kind of genetic damage associated with cancer, neurodegeneration and aging. It’s more difficult for cells to repair double-strand breaks than other kinds of DNA damage because there isn’t an intact “template” left to guide the reattachment of the strands.
Yet it’s also long been recognized that DNA breakage sometimes plays a constructive role, too. When cells are dividing, double-strand breaks allow for the normal process of genetic recombination between chromosomes. In the developing immune system, they enable pieces of DNA to recombine and generate a diverse repertoire of antibodies. Double-strand breaks have also been implicated in neuronal development and in helping turn certain genes on. Still, those functions have seemed like exceptions to the rule that double-strand breaks are accidental and unwelcome.
But a turning point came in 2015. Li-Huei Tsai, a neuroscientist and director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology, and her colleagues were following up on previous work that had linked Alzheimer’s disease with the accumulation of double-strand breaks in neurons. To their surprise, the researchers found that stimulating cultured neurons triggered double-strand breaks in their DNA, and the breaks quickly increased the expression of a dozen fast-acting genes associated with synaptic activity in learning and memory.
The double-strand breaks seemed to be essential for regulating gene activity important to the neurons’ function. Tsai and her collaborators hypothesized that the breaks essentially released enzymes that were stuck along twisted pieces of DNA, freeing them to transcribe relevant nearby genes quickly. But the idea “was met with a lot of skepticism,” Tsai said. “People simply have a hard time imagining that double-strand breaks can actually be physiologically important.”
Nevertheless, Paul Marshall, a postdoctoral researcher at the University of Queensland in Australia, and his colleagues decided to follow up on the finding. Their work, which appeared in 2019, both confirmed and extended the observations by Tsai’s team. It showed that the DNA breakage touched off two waves of enhanced gene transcription, one immediate and one several hours later.
Marshall and his colleagues proposed a two-step mechanism to explain the phenomenon: When the DNA breaks, some enzyme molecules are freed for transcription (as Tsai’s group suggested) and the site of the break is also chemically flagged with a methyl group, a so-called epigenetic marker. Later, when repair of the broken DNA begins, the marker is removed—and in the process, still more enzymes can spill free, starting the second round of transcription.
“Not only is the double-strand break involved as a trigger,” Marshall said, “it then becomes a marker, and that marker itself is functional in terms of regulating and guiding machinery to that location.”
Since then, other studies have demonstrated something similar. One, published last year, associated double-strand breaks not just with the formation of a fear memory, but with its recollection.
Now, in a study last month in PLOS ONE, Tsai and her colleagues have shown that this counterintuitive mechanism of gene expression might be prevalent in the brain. This time, instead of using cultured neurons, they looked at cells in the brains of living mice that were learning to associate an environment with an electric shock. When the team mapped genes undergoing double-strand breaks in the prefrontal cortex and hippocampus of mice that had been shocked, they found breaks occurring near hundreds of genes, many of which were involved in synaptic processes related to memory.
NAIROBI, Kenya (AP) — The body of Ugandan Olympic athlete Rebecca Cheptegei — who died after being set on fire by her partner in Kenya — was received Friday by family and anti-femicide crusaders, ahead of her burial a day later.
Cheptegei’s family met with dozens of activists Friday who had marched to the Moi Teaching and Referral Hospital’s morgue in the western city of Eldoret while chanting anti-femicide slogans.
She is the fourth female athlete to have been killed by her partner in Kenya in yet another case of gender-based violence in recent years.
Viola Cheptoo, the founder of Tirop Angels – an organization that was formed in honor of athlete Agnes Tirop, who was stabbed to death in 2021, said stakeholders need to ensure this is the last death of an athlete due to gender-based violence.
“We are here to say that enough is enough, we are tired of burying our sisters due to GBV,” she said.
It was a somber mood at the morgue as athletes and family members viewed Cheptegei’s body which sustained 80% of burns after she was doused with gasoline by her partner Dickson Ndiema. Ndiema sustained 30% burns on his body and later succumbed.
Ndiema and Cheptegei were said to have quarreled over a piece of land that the athlete bought in Kenya, according to a report filed by the local chief.
Cheptegei competed in the women’s marathon at the Paris Olympics less than a month before the attack. She finished in 44th place.
Cheptegei’s father, Joseph, said that the body will make a brief stop at their home in the Endebess area before proceeding to Bukwo in eastern Uganda for a night vigil and burial on Saturday.
“We are in the final part of giving my daughter the last respect,” a visibly distraught Joseph said.
He told reporters last week that Ndiema was stalking and threatening Cheptegei and the family had informed police.
Four in 10 women or an estimated 41% of dating or married Kenyan women have experienced physical or sexual violence perpetrated by their current or most recent partner, according to the Kenya Demographic and Health Survey 2022.
TEL AVIV, Israel (AP) — A rare Bronze-Era jar accidentally smashed by a 4-year-old visiting a museum was back on display Wednesday after restoration experts were able to carefully piece the artifact back together.
Last month, a family from northern Israel was visiting the museum when their youngest son tipped over the jar, which smashed into pieces.
Alex Geller, the boy’s father, said his son — the youngest of three — is exceptionally curious, and that the moment he heard the crash, “please let that not be my child” was the first thought that raced through his head.
The jar has been on display at the Hecht Museum in Haifa for 35 years. It was one of the only containers of its size and from that period still complete when it was discovered.
The Bronze Age jar is one of many artifacts exhibited out in the open, part of the Hecht Museum’s vision of letting visitors explore history without glass barriers, said Inbal Rivlin, the director of the museum, which is associated with Haifa University in northern Israel.
It was likely used to hold wine or oil, and dates back to between 2200 and 1500 B.C.
Rivlin and the museum decided to turn the moment, which captured international attention, into a teaching moment, inviting the Geller family back for a special visit and hands-on activity to illustrate the restoration process.
Rivlin added that the incident provided a welcome distraction from the ongoing war in Gaza. “Well, he’s just a kid. So I think that somehow it touches the heart of the people in Israel and around the world,“ said Rivlin.
Roee Shafir, a restoration expert at the museum, said the repairs would be fairly simple, as the pieces were from a single, complete jar. Archaeologists often face the more daunting task of sifting through piles of shards from multiple objects and trying to piece them together.
Experts used 3D technology, hi-resolution videos, and special glue to painstakingly reconstruct the large jar.
Less than two weeks after it broke, the jar went back on display at the museum. The gluing process left small hairline cracks, and a few pieces are missing, but the jar’s impressive size remains.
The only noticeable difference in the exhibit was a new sign reading “please don’t touch.”
VICTORIA – The British Columbia government is partnering with a bear welfare group to reduce the number of bears being euthanized in the province.
Nicholas Scapillati, executive director of Grizzly Bear Foundation, said Monday that it comes after months-long discussions with the province on how to protect bears, with the goal to give the animals a “better and second chance at life in the wild.”
Scapillati said what’s exciting about the project is that the government is open to working with outside experts and the public.
“So, they’ll be working through Indigenous knowledge and scientific understanding, bringing in the latest techniques and training expertise from leading experts,” he said in an interview.
B.C. government data show conservation officers destroyed 603 black bears and 23 grizzly bears in 2023, while 154 black bears were killed by officers in the first six months of this year.
Scapillati said the group will publish a report with recommendations by next spring, while an independent oversight committee will be set up to review all bear encounters with conservation officers to provide advice to the government.
Environment Minister George Heyman said in a statement that they are looking for new ways to ensure conservation officers “have the trust of the communities they serve,” and the panel will make recommendations to enhance officer training and improve policies.
Lesley Fox, with the wildlife protection group The Fur-Bearers, said they’ve been calling for such a committee for decades.
“This move demonstrates the government is listening,” said Fox. “I suspect, because of the impending election, their listening skills are potentially a little sharper than they normally are.”
Fox said the partnership came from “a place of long frustration” as provincial conservation officers kill more than 500 black bears every year on average, and the public is “no longer tolerating this kind of approach.”
“I think that the conservation officer service and the B.C. government are aware they need to change, and certainly the public has been asking for it,” said Fox.
Fox said there’s a lot of optimism about the new partnership, but, as with any government, there will likely be a lot of red tape to get through.
“I think speed is going to be important, whether or not the committee has the ability to make change and make change relatively quickly without having to study an issue to death, ” said Fox.
This report by The Canadian Press was first published Sept. 9, 2024.
