Recombination signal sequences are conserved sequences of noncoding DNA that are recognized by the RAG1/RAG2 enzyme complex during V(D)J recombination in immature B cells and T cells. [1] 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 and light-chain variable regions in T-cell receptors and immunoglobulin molecules. [1]
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.
[1]
[2] 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.
[3] Heptamer sequences are usually CACAGTG
and nonamers are usually ACAAAAACC
. The nucleotides in bold are more highly conserved.
[3] 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.
[1]
[2] This prevents two different genes coding for the same region from recombining (ex. V-V recombination).
[1] 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.
[1]
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. [1] 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. [1] [4] 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. [1] [4] This process is repeated for the joining of V to DJ. [1] In light-chain rearrangement, only V and J segments are brought together. [1]
Cryptic RSSs are gene sequences that resemble authentic RSSs and are occasionally mistaken for them by the RAG1/RAG2 enzyme complex. [3] Recombining an RSS with a cRSS can lead to chromosome translocations, which can lead to cancer. [3]
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 mutations. [5] [6] These infants will produce a non-functional RAG1/RAG2 enzyme complex that cannot recognize RSSs and therefore cannot initiate V(D)J recombination effectively. [5] [6] This disorder is characterized by a lack of functioning B and T cells. [1] [5]
Recombination signal sequences are conserved sequences of noncoding DNA that are recognized by the RAG1/RAG2 enzyme complex during V(D)J recombination in immature B cells and T cells. [1] 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 and light-chain variable regions in T-cell receptors and immunoglobulin molecules. [1]
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.
[1]
[2] 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.
[3] Heptamer sequences are usually CACAGTG
and nonamers are usually ACAAAAACC
. The nucleotides in bold are more highly conserved.
[3] 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.
[1]
[2] This prevents two different genes coding for the same region from recombining (ex. V-V recombination).
[1] 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.
[1]
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. [1] 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. [1] [4] 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. [1] [4] This process is repeated for the joining of V to DJ. [1] In light-chain rearrangement, only V and J segments are brought together. [1]
Cryptic RSSs are gene sequences that resemble authentic RSSs and are occasionally mistaken for them by the RAG1/RAG2 enzyme complex. [3] Recombining an RSS with a cRSS can lead to chromosome translocations, which can lead to cancer. [3]
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 mutations. [5] [6] These infants will produce a non-functional RAG1/RAG2 enzyme complex that cannot recognize RSSs and therefore cannot initiate V(D)J recombination effectively. [5] [6] This disorder is characterized by a lack of functioning B and T cells. [1] [5]