Immunity system complexity: developing new defenses (Introduction)

by David Turell @, Friday, September 13, 2019, 18:48 (8 days ago) @ David Turell

All our lives we must develop new defenses against newly contacted illnesses. This article tells us how it is done:

https://phys.org/news/2019-09-loops-dna-packaging-diverse-antibodies.html

" Diversity is good, especially when it comes to antibodies. It's long been known that a gene assembly process called V(D)J recombination allows our immune system to mix and match bits of genetic code, generating new antibodies to conquer newly encountered threats. But how these gene segments come together to be spliced has been a mystery.

"A pair of enzymes called RAG1 and RAG2, the researchers show, couple with mechanisms involved in making the chromatin loops to initiate the first step of V(D)J recombination—joining the D and J segments. The RAG 1/2 complex first binds to a site on an antibody gene known as the "recombination center." As the DNA scrolls past during the process of loop formation ("extrusion"), the RAG complex scans for the D and J segments the cell wants to combine. Other factors then impede the extrusion process, pausing the scrolling DNA at the recombination center so that RAG can access the desired segments.

"'The loop extrusion process is harnessed by antibody gene loci to properly present substrate gene segments to the RAG complex for V(D)J recombination," says Alt.

"While many of the hard-wired chromatin loops are formed and anchored by a factor known as CTCF, the Alt lab shows that other factors are involved in dynamic situations, like antibody formation, that require new loops on the fly. The study also establishes the role of a protein called cohesin in driving the loop extrusion/RAG scanning process.

"'While these findings have been made in the context of V(D)J recombination in antibody formation, they have implications for processes that could be involved in gene regulation more generally," says Alt."

Comment: Again a very necessary mechanism which is irreducibly complex and had to present from the beginning to offer disease protection or life would not have survived. More evidence for design


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