WordNet

place signs, as along a road; "sign an intersection"; "This road has been signed"
(medicine) any objective evidence of the presence of a disorder or disease; "there were no signs of asphyxiation"
a perceptible indication of something not immediately apparent (as a visible clue that something has happened); "he showed signs of strain"; "they welcomed the signs of spring" (同)mark
a character indicating a relation between quantities; "dont forget the minus sign"
a fundamental linguistic unit linking a signifier to that which is signified; "The bond between the signifier and the signified is arbitrary"--de Saussure
a gesture that is part of a sign language
a public display of a message; "he posted signs in all the shop windows"
engage by written agreement; "They signed two new pitchers for the next season" (同)contract, sign on, sign_up
approve and express assent, responsibility, or obligation; "All parties ratified the peace treaty"; "Have you signed your contract yet?" (同)ratify
communicate silently and non-verbally by signals or signs; "He signed his disapproval with a dismissive hand gesture"; "The diner signaled the waiters to bring the menu" (同)signal, signalize, signalise
mark with ones signature; write ones name (on); "She signed the letter and sent it off"; "Please sign here" (同)subscribe
be engaged by a written agreement; "He signed to play the casino on Dec. 18"; "The soprano signed to sing the new opera"
communicate in sign language; "I dont know how to sign, so I could not communicate with my deaf cousin"
determine the order of constituents in; "They sequenced the human genome"
a following of one thing after another in time; "the doctor saw a sequence of patients" (同)chronological sequence, succession, successiveness, chronological succession
film consisting of a succession of related shots that develop a given subject in a movie (同)episode
serial arrangement in which things follow in logical order or a recurrent pattern; "the sequence of names was alphabetical"; "he invented a technique to determine the sequence of base pairs in DNA"
several repetitions of a melodic phrase in different keys
arrange in a sequence
notably out of the ordinary; "the year saw one signal triumph for the Labour party"
an electric quantity (voltage or current or field strength) whose modulation represents coded information about the source from which it comes
any nonverbal action or gesture that encodes a message; "signals from the boat suddenly stopped" (同)signaling, sign
any incitement to action; "he awaited the signal to start"; "the victory was a signal for wild celebration"
(genetics) a combining of genes or characters different from what they were in the parents
(physics) a combining of charges or transfer of electrons in a gas that results in the neutralization of ions; important for ions arising from the passage of high-energy particles

PrepTutorEJDIC

(ある事実・状態・感情などの)『表れ』,印,気配,徴侯(indication);(…の)こん跡,計跡《+『of』+『名』》・『身ぶり』,手まね,合図 / 『標識』,看板 / (数学・音楽などの)記号 / (…の)『象徴』,シンボル(symbol)《+『of』+『名』》・《文》(…の)『前兆』,きざし《+『of』+『名』》・宮(きゅう)(黄道12区分の一つ) ・〈手紙・書類・作品など〉‘に'『署名する』・(…に)〈名前など〉‘を'書く《+『名』+『on』(『to』)+『名』》 / …‘を'雇う契約に署名する・…‘を'合図する,知らせる;…に合図する・署名する・契約書に署名して雇われる
〈U〉〈C〉(時間の上の,また因果関係のつながりによる)『連続』,続き / 〈C〉《a~》(…の)一連のもの《+『of』+『名』》 / 〈U〉(起こる)『順序』(order),筋道 / 〈C〉(…に対する)結果《+『to』+『名』》
(警告・指示・情報などを伝える)『信号』,合図 / (…の)きっかけ,動機,導火線《+『for』+『名』》 / 〈人・車など〉‘に'『合図する』,信号を送る / …‘を'『合図』(信号)『で知らせる』 / 『合図する』,信号する / 合図の,信号の / めざましい,顕著な

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/07/29 14:24:52」(JST)

wiki en

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]

Structure

Highly conserved regions of the heptamer and nonamer DNA sequences.

RSSs are made up of 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] Unlike spacer sequences, heptamer sequences are usually CACAGTG, and the first three nucleotides are highly conserved.^[3] Nonamers are usually ACAAAAACC, and the A/T basepairs are also 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]

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.

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]

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.^[3] Recombining an RSS with a cRSS can lead to chromosome translocations, which can lead to cancer.^[3]

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 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]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l Owen, Judith A.; Punt, Jenni; Stranford, Sharon A. (2013). Kuby Immunology. New York: W.H. Freeman and Company. pp. 233–235.
^ ^a ^b Schatz, David G.; Oettinger, Marjorie A.; Schlissel, Mark S. (1992). "V(D)J Recombination: Molecular Biology and Regulation". Annual Review Immunology. 10: 259–283.
^ ^a ^b ^c ^d ^e Roth, David B. (2014). "V(D)J Recombination: Mechanism, Errors, and Fidelity". Microbiology Spectrum: 1–11.
^ ^a ^b Rodgers, Karla (2017). "Riches in RAGs: Revealing the V(D)J Recombinase Through High-Resolution Structures". Cell Press. 42: 72–84.
^ ^a ^b ^c Buckley, Rebecca H. (2004). "Molecular Defects in Human Severe Combined Immunodeficiency And Approaches to Immune Reconstitution". Annual Review Immunology: 625–655.
^ ^a ^b Elnour, Ibtisam B; Ahmed, Shakeel; Halim, Kamel; Nirmala, V (2007). "Omenn's Syndrome: A rare primary immunodeficiency disorder". Sultan Qaboos University Medical Journal: 1–6.

UpToDate Contents

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1. T-B-NK+ SCID：病因および遺伝学 t b nk scid pathogenesis and genetics
2. T細胞受容体の遺伝学 t cell receptor genetics
3. 免疫遺伝学 immunoglobulin genetics
4. 重度複合型免疫不全（SCID）：特定の欠損 severe combined immunodeficiency scid specific defects
5. 複合免疫不全 combined immunodeficiencies

English Journal

Secretome analysis of Glioblastoma cell line - HNGC-2.

Gupta MK, Polisetty RV, Ramamoorthy K, Tiwary S, Kaur N, Uppin MS, Shiras A, Sirdeshmukh R.SourceCentre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad, 500007, India.
Molecular bioSystems.Mol Biosyst.2013 Mar 13. [Epub ahead of print]
Glioblastoma multiforme (GBM) is the most common and aggressive type of primary malignant tumor of the central nervous system. We have carried out a deep analysis of the secretome of a rapidly proliferating and tumorigenic cell line HNGC-2, representing GBM, in an effort to identify proteins, which
PMID 23483059

Concurrent V(D)J recombination and DNA end instability increase interchromosomal trans-rearrangements in ATM-deficient thymocytes.

Bowen S, Wangsa D, Ried T, Livak F, Hodes RJ.SourceDepartment of Microbiology and Immunology, Graduate Program in Life Sciences, University of Maryland Baltimore, Baltimore, MD 21201, USA, Experimental Immunology Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA, Genetics Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA and Marlene and Stuart Greenebaum Cancer Center, University of Maryland, Baltimore, MD 21201, USA.
Nucleic acids research.Nucleic Acids Res.2013 Mar 6. [Epub ahead of print]
During the CD4-CD8- (DN) stage of T-cell development, RAG-dependent DNA breaks and V(D)J recombination occur at three T-cell receptor (TCR) loci: TCRβ, TCRγ and TCRδ. During this stage, abnormal trans-rearrangements also take place between TCR loci, occurring at increased frequency in absence of
PMID 23470994

Transcription-coupled eviction of histones H2A/H2B governs V(D)J recombination.

Bevington S, Boyes J.SourceInstitute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
The EMBO journal.EMBO J.2013 Mar 5. doi: 10.1038/emboj.2013.42. [Epub ahead of print]
Initiation of V(D)J recombination critically relies on the formation of an accessible chromatin structure at recombination signal sequences (RSSs) but how this accessibility is generated is poorly understood. Immunoglobulin light-chain loci normally undergo recombination in pre-B cells. We show here
PMID 23463099