A novel DNA damage alarm

June 25, 2015, HorizonHealth

How does our body keep its DNA intact? Researchers at Erasmus MC have just found a new piece of this puzzle. They discovered a novel alarm that cells use to signal DNA damage. "We already knew that DNA damage triggers an alarm in our body cells", says lead researcher Wim Vermeulen. "We have now shown that this alarm is also set off during transcription (expression) of damaged genes." Maria Tresini, Jurgen Marteijn, Wim Vermeulen and other co-workers just published their findings in the leading scientific journal Nature.

Cellular metabolic byproducts, chemicals, and radiation such as sunlight continually our DNA. Damaged DNA disturbs cellular function and can cause ageing. Moreover, permanent changes in the genetic code (i.e. mutations) can arise when the DNA duplicates before the error is repaired. Mutations may result in cancer. Fortunately, most lesions are quickly repaired by the cell's repair proteins. In addition, the cell turns on a DNA damage alarm when it detects DNA lesions.

DNA damage response

The alarm sets a variety of processes in motion. For instance, it temporarily stops DNA duplication and cell division, preventing errors from being passed on to daughter cells. But DNA damage does not only affect DNA duplication, it also has a great impact on gene transcription (the process that copies DNA into RNA, which is necessary for gene expression). The enzyme that carries out transcription halts when it encounters a UV-induced DNA lesion. Dr Maria Tresini: "Until now, it was unknown whether these transcription problems also trigger the DNA damage response. We discovered that this is indeed the case."

ATM protein

The key actor in the new mechanism is a protein called "ATM". It has long been known that ATM has a central role in DNA damage signal transmission when DNA double strand breaks are formed. "But now we found that the ATM alarm is also triggered by UV-induced halting. ATM then influences alternative splicing of gene transcripts. This leads to the formation of new protein variants that may counteract the negative effects of DNA lesions", says Dr Jurgen Marteijn.

Solving the puzzle

Professor Vermeulen concludes: "This is an important step towards solving the complex puzzle of how respond to DNA damage to protect us from ageing and cancer. Our study provides opportunities for possible intervention in these important medical problems in the future."

Explore further: Researchers clarify how DNA damage signaling works

More information: On the web portal HorizonHealth.eu, they explain how the novel DNA damage alarm works: www.horizonhealth.eu/dna-damage-alarm

The core spliceosome as target and effector of non-canonical ATM signalling, Nature (2015) DOI: 10.1038/nature14512

Related Stories

Researchers clarify how DNA damage signaling works

March 31, 2015

The DNA molecule is chemically unstable, giving rise to DNA lesions of various kinds. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed. The DNA damage response ...

Sall4 is required for DNA repair in stem cells

March 2, 2015

A protein that helps embryonic stem cells (ESCs) retain their identity also promotes DNA repair, according to a study in The Journal of Cell Biology. The findings raise the possibility that the protein, Sall4, performs a ...

Recommended for you

Floodplain forests under threat

March 19, 2019

A team from the Institute of Forest Sciences at the University of Freiburg shows that the extraction of ground water for industry and households is increasingly damaging floodplain forests in Europe given the increasing intensity ...

Scientists discover common blueprint for protein antibiotics

March 19, 2019

A discovery by researchers at the Los Angeles Biomedical Research Institute (LA BioMed) has uncovered a common blueprint for proteins that have antimicrobial properties. This finding opens the door to design and development ...

Nanoscale Lamb wave-driven motors in nonliquid environments

March 19, 2019

Light driven movement is challenging in nonliquid environments as micro-sized objects can experience strong dry adhesion to contact surfaces and resist movement. In a recent study, Jinsheng Lu and co-workers at the College ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.