FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2979020199> ?p ?o ?g. }

• W2979020199 abstract "Developing lymphocytes in the immune system of jawed vertebrates assemble antigen-receptor genes by undergoing large-scale reorganization of spatially separated V, D, and J gene segments through a process known as V(D)J recombination. The RAG protein initiates this process by binding and cutting recombination signal sequences (RSSs) composed of conserved heptamer and nonamer sequences flanking less well-conserved 12- or 23-bp spacers. Little quantitative information is known about the contributions of individual RSS positions over the course of the RAG-RSS interaction. We employ a single-molecule method known as tethered particle motion to quantify the formation, stability, and cleavage of the RAG-12RSS-23RSS paired complex (PC) for numerous synthetic and endogenous 12RSSs. We thoroughly investigate the sequence space around a RSS by making 40 different single-bp changes and characterizing the reaction dynamics. We reveal that single-bp changes affect RAG function based on their position: loss of cleavage function (first three positions of the heptamer); reduced propensity for forming the PC (the nonamer and last four bp of the heptamer); or variable effects on PC formation (spacer). We find that the rare usage of some endogenous gene segments can be mapped directly to their adjacent 12RSSs to which RAG binds weakly. The 12RSS, however, cannot explain the high-frequency usage of other gene segments. Finally, we find that RSS nicking, while not required for PC formation, substantially stabilizes the PC. Our findings provide detailed insights into the contribution of individual RSS positions to steps of the RAG-RSS re-action that previously have been difficult to assess quantitatively. Summary V(D)J recombination is a genomic cut-and-paste process for generating diverse antigen-receptor repertoires. The RAG enzyme brings separate gene segments together by binding the neighboring sequences called RSSs, forming a paired complex (PC) before cutting the DNA. There are limited quantitative studies of the sequence-dependent dynamics of the crucial inter-mediate steps of PC formation and cleavage. Here, we quantify individual RAG-DNA dynamics for various RSSs. While RSSs of frequently-used segments do not comparatively enhance PC formation or cleavage, the rare use of some segments can be explained by their neighboring RSSs crippling PC formation and/or cleavage. Furthermore, PC lifetimes reveal DNA-nicking is not required for forming the PC, but PCs with nicks are more stable." @default.
• W2979020199 created "2019-10-10" @default.
• W2979020199 creator A5005364757 @default.
• W2979020199 creator A5029612834 @default.
• W2979020199 creator A5042763205 @default.
• W2979020199 creator A5064898282 @default.
• W2979020199 creator A5072133463 @default.
• W2979020199 creator A5078106255 @default.
• W2979020199 creator A5085836367 @default.
• W2979020199 creator A5088151758 @default.
• W2979020199 date "2019-10-04" @default.
• W2979020199 modified "2023-09-23" @default.
• W2979020199 title "Sequence-Dependent Dynamics of Synthetic and Endogenous RSSs in V(D)J Recombination" @default.
• W2979020199 cites W1869519490 @default.
• W2979020199 cites W1967867591 @default.
• W2979020199 cites W1971804853 @default.
• W2979020199 cites W1976310910 @default.
• W2979020199 cites W1977764826 @default.
• W2979020199 cites W1983450672 @default.
• W2979020199 cites W2009224491 @default.
• W2979020199 cites W2022372517 @default.
• W2979020199 cites W2025592993 @default.
• W2979020199 cites W2045057008 @default.
• W2979020199 cites W2047012085 @default.
• W2979020199 cites W2058660996 @default.
• W2979020199 cites W2078037305 @default.
• W2979020199 cites W2079416470 @default.
• W2979020199 cites W2082950657 @default.
• W2979020199 cites W2084354924 @default.
• W2979020199 cites W2087604899 @default.
• W2979020199 cites W2088987673 @default.
• W2979020199 cites W2090039478 @default.
• W2979020199 cites W2096019013 @default.
• W2979020199 cites W2100213817 @default.
• W2979020199 cites W2100879474 @default.
• W2979020199 cites W2101335905 @default.
• W2979020199 cites W2104237021 @default.
• W2979020199 cites W2110510545 @default.
• W2979020199 cites W2111765906 @default.
• W2979020199 cites W2117789925 @default.
• W2979020199 cites W2117878894 @default.
• W2979020199 cites W2125622789 @default.
• W2979020199 cites W2129547595 @default.
• W2979020199 cites W2129745108 @default.
• W2979020199 cites W2129962602 @default.
• W2979020199 cites W2142405966 @default.
• W2979020199 cites W2147806005 @default.
• W2979020199 cites W2153230724 @default.
• W2979020199 cites W2154969423 @default.
• W2979020199 cites W2157852081 @default.
• W2979020199 cites W2163396356 @default.
• W2979020199 cites W2167216803 @default.
• W2979020199 cites W2192556660 @default.
• W2979020199 cites W2414054851 @default.
• W2979020199 cites W2528408357 @default.
• W2979020199 cites W2578150941 @default.
• W2979020199 cites W2803234572 @default.
• W2979020199 cites W2895519614 @default.
• W2979020199 cites W2973094225 @default.
• W2979020199 cites W4245455447 @default.
• W2979020199 doi "https://doi.org/10.1101/791954" @default.
• W2979020199 hasPublicationYear "2019" @default.
• W2979020199 type Work @default.
• W2979020199 sameAs 2979020199 @default.
• W2979020199 citedByCount "1" @default.
• W2979020199 countsByYear W29790201992020 @default.
• W2979020199 crossrefType "posted-content" @default.
• W2979020199 hasAuthorship W2979020199A5005364757 @default.
• W2979020199 hasAuthorship W2979020199A5029612834 @default.
• W2979020199 hasAuthorship W2979020199A5042763205 @default.
• W2979020199 hasAuthorship W2979020199A5064898282 @default.
• W2979020199 hasAuthorship W2979020199A5072133463 @default.
• W2979020199 hasAuthorship W2979020199A5078106255 @default.
• W2979020199 hasAuthorship W2979020199A5085836367 @default.
• W2979020199 hasAuthorship W2979020199A5088151758 @default.
• W2979020199 hasBestOaLocation W29790201991 @default.
• W2979020199 hasConcept C104317684 @default.
• W2979020199 hasConcept C111919701 @default.
• W2979020199 hasConcept C113646796 @default.
• W2979020199 hasConcept C14036430 @default.
• W2979020199 hasConcept C151730666 @default.
• W2979020199 hasConcept C153911025 @default.
• W2979020199 hasConcept C156695909 @default.
• W2979020199 hasConcept C157402786 @default.
• W2979020199 hasConcept C16613235 @default.
• W2979020199 hasConcept C175156509 @default.
• W2979020199 hasConcept C2385561 @default.
• W2979020199 hasConcept C41008148 @default.
• W2979020199 hasConcept C43369102 @default.
• W2979020199 hasConcept C54355233 @default.
• W2979020199 hasConcept C55493867 @default.
• W2979020199 hasConcept C70721500 @default.
• W2979020199 hasConcept C86803240 @default.
• W2979020199 hasConcept C95444343 @default.
• W2979020199 hasConceptScore W2979020199C104317684 @default.
• W2979020199 hasConceptScore W2979020199C111919701 @default.
• W2979020199 hasConceptScore W2979020199C113646796 @default.
• W2979020199 hasConceptScore W2979020199C14036430 @default.
• W2979020199 hasConceptScore W2979020199C151730666 @default.
• W2979020199 hasConceptScore W2979020199C153911025 @default.

• next