Early in the life of B lymphocytes -- the immune cells responsible for hunting down foreign invaders and labeling them for destruction -- they rearrange their DNA to create various surface receptors that can accurately identify different intruders, a process called V(D)J recombination. Now, in an study published online today in the journal Cell, Rockefeller University Professor Michel Nussenzweig, in collaboration with his brother André Nussenzweig at NCI and their colleagues, shows that when the ATM protein is absent, chromosomal breaks created during V(D)J recombination go unrepaired, and checkpoints that normally prevent the damaged cell from replicating are lost.
Normal lymphocytes contain a number of restorative proteins, whose job it is to identify chromosomal damage and repair it or, if the damage is irreparable, prevent the cell from multiplying. Earlier research by André and Michel Nussenzweig, who is an investigator at HHMI, had identified other DNA repair proteins that are important during different phases of a B lymphocyte's life. It was during one of these studies, which examined genetic damage late in the life of a B cell, that they came across chromosomal breaks that could not be explained.
So the researchers began to look into the potential role of V(D)J recombination. "We were not expecting it to be responsible for the breaks we were seeing," says Michel, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology. "Because for it to be responsible, the breaks would have had to happen early on, the cell would have to divide, mature, maintain the breaks, and stay alive with broken chromosomes."
This, in fact, was precisely what they found.
The ATM protein appears to have two roles in a B cell: It helps repair the DNA double-strand breaks, and it activates the cell-cycle checkpoint that prevents genetically damaged cells from dividing. "ATM is required for a B cell to know that it has a broken chromosome. And if it doesn't know that it seems to be able to keep on going," says Michel.
Since the ATM protein is mutated in a number of lymphomas -- cancers of the lymph and immune system -- the new finding suggests to researchers that the lymphocytes could have been living with DNA damage for a long time, and that this damage likely plays a role in later chromosomal translocations, rearrangements of genetic materials that can lead to cancer.
Michel and his brother, who've been collaborators for more than a decade, intend to pursue the molecular mechanisms by which these chromosomal translocations occur. "I think it's important to understand them," he says, "because eventually we might be able to prevent these dangerous chromosome fusions."
Joseph Bonner | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy