Regulating infidelity: RNA‐mediated recruitment of AID to DNA during class switch recombination

DiMenna, Lauren J.; Chaudhuri, Jayanta

doi:10.1002/eji.201545809

Cited by 5 publications

(4 citation statements)

References 84 publications

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“…APE1 is the endonuclease utilized during BER. After OGG1 generates an AP site [163] APE1 binds to this region [164,165]. Genome-wide mapping of APE1-and OGG1-binding sites revealed a significant overlap to G4 motifs [84].…”

Section: Base Excision Repair (Ber)mentioning

confidence: 99%

The Relevance of G-Quadruplexes for DNA Repair

Linke

Limmer

Juranek

et al. 2021

IJMS

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DNA molecules can adopt a variety of alternative structures. Among these structures are G-quadruplex DNA structures (G4s), which support cellular function by affecting transcription, translation, and telomere maintenance. These structures can also induce genome instability by stalling replication, increasing DNA damage, and recombination events. G-quadruplex-driven genome instability is connected to tumorigenesis and other genetic disorders. In recent years, the connection between genome stability, DNA repair and G4 formation was further underlined by the identification of multiple DNA repair proteins and ligands which bind and stabilize said G4 structures to block specific DNA repair pathways. The relevance of G4s for different DNA repair pathways is complex and depends on the repair pathway itself. G4 structures can induce DNA damage and block efficient DNA repair, but they can also support the activity and function of certain repair pathways. In this review, we highlight the roles and consequences of G4 DNA structures for DNA repair initiation, processing, and the efficiency of various DNA repair pathways.

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Section: Base Excision Repair (Ber)mentioning

confidence: 99%

The Relevance of G-Quadruplexes for DNA Repair

Linke

Limmer

Juranek

et al. 2021

IJMS

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“…Intronic switch RNAs were known to be spliced from primary transcripts to form lariats that undergo hydrolytic degradation, which is catalyzed by the debranching enzyme DBR1 49 . Knockdown of DBR1 in CH12F3 cells reduces CSR; however, expression of switch RNAs in trans bypasses the lariat debranching step in DBR1 knockdown cells to rescue both CSR and AID recruitment to S regions in a sequence-specific manner 33 , 50 . In addition, AID bound directly and selectively to sense S-region transcripts, which were shown to form highly stable four-stranded G4 structures 33 , 50 .…”

Section: Aid Targeting To Switch Regionsmentioning

confidence: 99%

“…Knockdown of DBR1 in CH12F3 cells reduces CSR; however, expression of switch RNAs in trans bypasses the lariat debranching step in DBR1 knockdown cells to rescue both CSR and AID recruitment to S regions in a sequence-specific manner 33 , 50 . In addition, AID bound directly and selectively to sense S-region transcripts, which were shown to form highly stable four-stranded G4 structures 33 , 50 . A putative G4 RNA binding motif in AID was identified and mutations in this domain abrogated AID interactions with G4 switch RNA and consequently the localization of AID to S regions and wild-type levels of CSR 33 , 50 .…”

Section: Aid Targeting To Switch Regionsmentioning

confidence: 99%

“…In addition, AID bound directly and selectively to sense S-region transcripts, which were shown to form highly stable four-stranded G4 structures 33 , 50 . A putative G4 RNA binding motif in AID was identified and mutations in this domain abrogated AID interactions with G4 switch RNA and consequently the localization of AID to S regions and wild-type levels of CSR 33 , 50 . Interestingly, a mutation in the RNA binding motif of AID (G133V) has been identified in patients with Hyper-IgM Syndrome who show severe CSR defects 51 .…”

Section: Aid Targeting To Switch Regionsmentioning

confidence: 99%

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Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

et al. 2018

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Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR. Within the Ig locus, DNA repair pathways are diverted from their canonical role in maintaining genomic integrity to permit AID-directed mutation and deletion of gene coding segments. Recently identified proteins, genes, and regulatory networks have provided new insights into the temporally and spatially coordinated molecular interactions that control the formation and repair of DSBs within the Ig locus. Unravelling the genetic program that allows B cells to selectively alter the Ig coding regions while protecting non-Ig genes from DNA damage advances our understanding of the molecular processes that maintain genomic integrity as well as humoral immunity.

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Diversity of Immunoglobulin (Ig) Isotypes and the Role of Activation-Induced Cytidine Deaminase (AID) in Fish

et al. 2018

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The disparate diversity in immunoglobulin (Ig) repertoire has been a subject of fascination since the emergence of prototypic adaptive immune system in vertebrates. The carboxy terminus region of activation-induced cytidine deaminase (AID) has been well established in tetrapod lineage and is crucial for its function in class switch recombination (CSR) event of Ig diversification. The absence of CSR in the paraphyletic group of fish is probably due to changes in catalytic domain of AID and lack of cis-elements in IgH locus. Therefore, understanding the arrangement of Ig genes in IgH locus and functional facets of fish AID opens up new realms of unravelling the alternative mechanisms of isotype switching and antibody diversity. Further, the teleost AID has been recently reported to have potential of catalyzing CSR in mammalian B cells by complementing AID deficiency in them. In that context, the present review focuses on the recent advances regarding the generation of diversity in Ig repertoire in the absence of AID-regulated class switching in teleosts and the possible role of T cell-independent pathway involving B cell activating factor and a proliferation-inducing ligand in activation of CSR machinery.

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Regulating infidelity: RNA‐mediated recruitment of AID to DNA during class switch recombination

Cited by 5 publications

References 84 publications

The Relevance of G-Quadruplexes for DNA Repair

The Relevance of G-Quadruplexes for DNA Repair

Generating and repairing genetically programmed DNA breaks during immunoglobulin class switch recombination

Diversity of Immunoglobulin (Ig) Isotypes and the Role of Activation-Induced Cytidine Deaminase (AID) in Fish

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