Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Solve Another Mystery in B Lymphocyte Development

25.05.2009
A new study published online in Nature Immunology ahead of the June 2009 print issue has found that homologous immunoglobulin (lg) alleles pair up in the nucleus at stages that coincide with V(D)J recombination of the heavy and light chain (Igh and Igk) loci.

Researchers led by Jane A. Skok Ph.D., assistant professor in the Department of Pathology at NYU School of Medicine and a member of the NYU Cancer Institute, showed that the V(D)J recombinase, which consists of the RAG1 and RAG2 proteins, mediates this pairing and helps ensure that only one allele undergoes recombination at a time (a process known as allelic exclusion).

In “RAG-1 and ATM Coordinate Monoallelic Recombination and Nuclear Positioning of Immunoglobulin Loci,” researchers found that RAG-mediated cleavage occurs on one allele at a time at every stage of Igh and Igk recombination; introduction of a double-strand break on one lg allele induces repositioning of its homologous partner to pericentromeric heterochromatin (a repressive compartment of the nucleus). This repositioning, surprisingly enough, depends on the DNA damage sensing factor ATM. It appears that cleavage activates ATM to act in trans on the uncleaved allele to reposition it in a repressive compartment of the nucleus, thereby preventing simultaneous recombination on both alleles and thus reducing the chance of translocations.

“This work deepens our understanding of the mechanisms that are in place for preventing translocations during V(D)J recombination that might ultimately lead to leukemias and lymphomas,” says Skok. “It also helps us understand why individuals with a genetic deficiency in ATM suffer more cancers arising from such translocations.”

Leukemias and lymphomas are very common cancers, especially in children. Chromosomal translocations involving the antigen receptor loci are a common underlying mechanism.

“V(D)J recombination plays a crucial role in the development of the immune system,” says Skok. “But because it entails the repeated cutting and joining of DNA gene segments, it carries a risk of translocation.”

Skok says that given the deleterious consequences, it is essential that B and T cells tightly regulate the recombinase, the accessibility of substrates for RAG cleavage, and the activities of the DNA damage response and repair machineries. Skok and researchers propose that homologous pairing of alleles undergoing recombination has a number of functions: (i) To protect genomic stability by ensuring that broken ends are aligned with homologous alleles rather than in contact with other loci. (ii) To provide a means for repair proteins recruited to sites of DSBs to act in trans on the uncleaved allele to prevent simultaneous cleavage on the latter. (iii) To ensure sequential recombination of individual alleles to help maintain allelic exclusion. In this sense homologous pairing of Ig alleles is analogous to pairing of X chromosomes which has an important role in X inactivation in developing female cells. The data suggest that in parallel with X inactivation, homologous pairing of Ig loci contributes to allelic exclusion by ensuring that only one allele is targeted for recombination at any time.

Dorie Klissas | Newswise Science News
Further information:
http://www.med.nyu.edu

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>