Recombination signal sequences are

conserved sequence In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ...

s of

noncoding DNA Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regu ...

that are recognized by the RAG1/RAG2 enzyme complex during

V(D)J recombination V(D)J recombination (variable–diversity–joining rearrangement) is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire ...

in immature

B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

s and

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s. Recombination signal sequences guide the enzyme complex to the V, D, and J gene segments that will undergo recombination during the formation of the

heavy Heavy may refer to: Measures * Heavy, a characterization of objects with substantial weight * Heavy, a wake turbulence category used by pilots and air traffic controllers to refer to aircraft with a maximum takeoff mass of 136,000 kgs or mo ...

and light-chain variable regions in

T-cell receptor The T-cell receptor (TCR) is a protein complex, located on the surface of T cells (also called T lymphocytes). They are responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. ...

s and immunoglobulin molecules.

Structure

RSSs are made up of highly conserved heptamer sequences (7 base pairs), spacer sequences, and conserved nonamer sequences (9 base pairs) that are adjacent to the V, D and J sequences in the heavy-chain region of DNA and the V and J sequences in the light-chain DNA region. Spacer sequences are located between heptamer and nonamer sequences and exhibit base pair variety but are always either 12 base pairs or 23 base pairs long. Heptamer sequences are usually CACAGTG and nonamers are usually ACAAAAACC. The nucleotides in bold are more highly conserved. The RAG1/RAG2 enzyme complex follows the 12-23 rule when joining V, D, and J segments, pairing 12-bp spacer RSSs to 23-bp spacer RSSs. This prevents two different genes coding for the same region from recombining (ex. V-V recombination). RSSs are located between V, D, and J segments of the germ-line DNA of maturing B and T lymphocytes and are permanently spliced out of the final Ig mRNA product after V(D)J recombination is complete.

Function

The RAG1/RAG2 enzyme complex recognizes the heptamer sequences flanking the V and J coding regions and nicks their 5' end, releasing the intervening DNA between the V and J coding regions. In the heavy-chain coding region of DNA, the RAG1/RAG2 enzyme complex recognizes the RSSs flanking the D and J segments and brings them together, forming a loop containing intervening DNA. The RAG1/RAG2 complex then introduces a nick at the 5' end of the RSS heptamers adjacent to the coding regions on both the D and J segments, permanently removing the loop of intervening DNA and creating a double-stranded break that is repaired by VDJ recombinase enzymes. This process is repeated for the joining of V to DJ. In light-chain rearrangement, only V and J segments are brought together.

Related Diseases & Disorders

cRSS

Cryptic RSSs are gene sequences that resemble authentic RSSs and are occasionally mistaken for them by the RAG1/RAG2 enzyme complex. Recombining an RSS with a cRSS can lead to chromosome translocations, which can lead to cancer.

Omenn's Syndrome

Some infants born with autosomal recessive SCIDS lack a functional copies of the genes that code for the RAG1/RAG2 enzyme complex because of

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn alt ...

s. These infants will produce a non-functional RAG1/RAG2 enzyme complex that cannot recognize RSSs and therefore cannot initiate V(D)J recombination effectively. This disorder is characterized by a lack of functioning B and T cells.

References

{{Reflist Immune system