Journal News

JBC: Researchers clock DNA’s recovery time

Jonathan Griffin
Nov. 1, 2019

In the time it takes for an Amazon Prime delivery to arrive, cells damaged by chemotherapy can fix their most important DNA almost completely. That’s true in mouse livers mice at least, according to a new study.

Circadian rhythmicity of metabolic processesCircadian rhythmicity of metabolic processes has a significant impact on physiology and behavior. National Human Genome Research Institute

Researchers found that DNA damaged by the chemotherapy drug cisplatin is mostly good as new in noncancerous tissue within two circadian cycles, or two days. The results, published in the Journal of Biological Chemistry, could inform strategies for administering chemotherapy at times that maximize tumor damage while minimizing side effects.

Side effects of cisplatin include kidney, liver and peripheral nerve injury. Cisplatin kills cells, cancerous or not, by damaging their DNA, so Nobel laureate Aziz Sancar and his team aimed to uncover the pattern of DNA repair in healthy cells. In normal cells, the circadian clock drives the rhythm of DNA repair, but not in tumors.

“Most cancers do not have a functional clock and so, basically any time that it’s good for the normal tissue, you can hit the cancer,” said Sancar, a professor at the University of North Carolina School of Medicine.

In an earlier study, Sancar’s team looked at DNA repair across a mouse genome, uncovering two mechanisms of circadian-controlled DNA repair.

They found that for some genes, transcription — during which damaged DNA is recognized and patched up — was controlled by the circadian clock. The pattern was specific to each gene, with repair peaking at different times of day. For the remaining DNA that is not transcribed or expressed, repair was less efficient but also clock-controlled, and maximum repair occurred between 4 p.m. and 6 p.m., Sancar said.

In this previous experiment, they examined DNA two hours after injecting cisplatin, but in their new work in JBC, Sancar’s team wanted to study recovery on a more clinically relevant time scale.

Patients get cisplatin intravenously at weekly, 10-day or two week intervals, allowing recovery time between doses, Sancar explained. “And so we wanted to know what happens over those long periods.”

Using a technique developed in their lab, the team captured and sequenced fragments of damaged DNA from mice injected with cisplatin. Over 70 days, they produced maps displaying where and when DNA was fixed at the resolution of a single nucleotide.

The DNA of transcribed genes was just about fully mended in two circadian cycles, Sancar said. Most repair in the first 48 hours was to these genes.

The remaining damage in nontranscribed DNA is not harmful in normal cells that aren’t replicating, Sancar said. But for cancer cells, which divide uncontrollably, this damage could lead to cell death.

Before this information is considered in the clinic, further experiments are needed, Sancar said.

Sancar is working with oncologists, evaluating new cisplatin regimens in mice implanted with human tumors to find a treatment that reduces toxicity in normal tissue while hitting cancer hard.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition weekly.

Learn more
Jonathan Griffin

Jonathan Griffin is a science communicator for all ASBMB journals. Follow him on Twitter.

Related articles

From the journals: March 2019
John Arnst, Courtney Chandler, Isha Dey & Catherine Goodman
From the journals: JBC
Emily Ulrich
From the Journals: JBC
Ken Farabaugh
No oxygen? No problem
Marissa Locke Rottinghaus

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Guiding grocery carts to shape healthy habits
Award

Guiding grocery carts to shape healthy habits

Nov. 21, 2024

Robert “Nate” Helsley will receive the Walter A. Shaw Young Investigator in Lipid Research Award at the 2025 ASBMB Annual Meeting, April 12–15 in Chicago.

Quantifying how proteins in microbe and host interact
Journal News

Quantifying how proteins in microbe and host interact

Nov. 20, 2024

“To develop better vaccines, we need new methods and a better understanding of the antibody responses that develop in immune individuals,” author Johan Malmström said.

Leading the charge for gender equity
Award

Leading the charge for gender equity

Nov. 19, 2024

Nicole Woitowich will receive the ASBMB Emerging Leadership Award at the 2025 ASBMB Annual meeting, April 12–15 in Chicago.

CRISPR gene editing: Moving closer to home
News

CRISPR gene editing: Moving closer to home

Nov. 17, 2024

With the first medical therapy approved, there’s a lot going on in the genome editing field, including the discovery of CRISPR-like DNA-snippers called Fanzors in an odd menagerie of eukaryotic critters.

Finding a missing piece for neurodegenerative disease research
News

Finding a missing piece for neurodegenerative disease research

Nov. 16, 2024

Ursula Jakob and a team at the University of Michigan have found that the molecule polyphosphate could be what scientists call the “mystery density” inside fibrils associated with Alzheimer’s, Parkinson’s and related conditions.

From the journals: JLR
Journal News

From the journals: JLR

Nov. 15, 2024

Enzymes as a therapeutic target for liver disease. Role of AMPK in chronic liver disease Zebrafish as a model for retinal dysfunction. Read about the recent JLR papers on these topics.