Search

NHEJ is the primary repair pathway during class switch recombination. Here the authors show that in absence of NHEJ, Pol θ repairs persistent G1-induced breaks in S-phase resulting in recombination products showing resection and microhomology.

Antigen receptor diversity relies on careful DNA cleavage and repair. Here the authors identify a functional interplay between RAG2 and XLF during V(D)J recombination, revealing an important role for the RAG complex in repairing induced DNA double-strand breaks and maintaining genome integrity.

Mice lacking the C-terminal non-core domain of RAG2 and ATM mutant mice develop thymic lymphomas harbouring recurrentTcra/d–Ightranslocations. Here the authors show that ATM and the non-core domain of RAG2 prevent bi-locus recombination by modulating higher-order chromatin structure.

SHLD1, as a component of the Shieldin (SHLD) complex, mediates DNA repair via non-homologous end-joining (NHEJ), an essential process during lymphocyte development. Here the authors show that SHLD1 is actually dispensable for lymphocyte development and V(D)J recombination, but is essential for class-switching recombination in activated B cells.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Depending on the cell cycle stage, cells can repair their genome via different pathways. Here the authors reveal mechanistic insights into repair of double strand breaks induced during G1 in an error-prone manner by Pol θ-dependent and PARP1-independent alt NHEJ during the SG2/M phases of the cell cycle

Through CRISPR–Cas9 screen, Dev et al. identified that SHLD1/2 inhibition contributes to PARP-inhibitor resistance. Mechanistically, SHLDs promote non-homologous end-joining and antagonize homologous recombination.

In the process of generating antibody diversity, DNA in the V(D)J locus undergoes programmed double-strand breaks that are made by the Rag1–Rag 2 complex. These breaks are repaired by the non-homologous end-joining (NHEJ) pathway. Cells deficient in NHEJ factors show very low levels of recombinants, so it was believed there might be another repair pathway. But this paper shows that an alternative NHEJ pathway exists, and that it functions at low levels even in wild-type cells.

FAM72A interacts with UNG2 to regulate the balance between error-prone and error-free DNA repair.

MAD2L2 — a member of the shieldin complex — is known to play important roles in DNA repair. Here the authors demonstrate how MAD2L2 dimerization mediated through SHLD2 participates in shieldin assembly and function.

A survey of 136 factors that may influence cytokine secretion identify smoking, cytomegalovirus latent infection and body mass index as influential factors, with varying effects on innate and adaptive immunity.

Misrepair of DNA double strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin and T-cell receptor loci has been implicated in the pathogenesis of lymphoid malignancies. Here, the RAG2 carboxy terminus is shown to be critical for maintaining genomic stability. Rag2^c/c p53^−/− mice, unlike Rag1^c/c p53^−/− and p53^−/− mice, rapidly develop thymic lymphomas bearing complex chromosomal translocations, amplifications and deletions involving the Tcrα/δ and Igh loci. These results reveal a new 'genome guardian' role for RAG2 and suggest that similar 'end release/end persistence' mechanisms underlie genomic instability and lymphomagenesis in Rag2^c/c p53^−/− and Atm^−/− mice.

Bloch et al., develop a high-throughput multiplex serological assay using bead-based Luminex technology to measure antibodies to a broad panel of vaccine-preventable diseases and common viral infections. They find a high level of population-level immunity to respiratory viruses and vaccine-preventable diseases, but with some notable immunity gaps in young children.

Co-abundance analysis of 938 healthy individuals uncovers how host factors shape gut microbiome interactions, highlighting a core set of 200 impacted genera and additional factor-specific interactions.

Many studies assess epigenetic marks in white blood cells, but it is unclear how much immune factors affect the epigenome. Here, the authors show that fine-scale blood cell composition and cytomegalovirus infection affect the DNA methylome of adults.

Derivation of human induced pluripotent stem cells (hiPSCs) produces primed hiPSCs that can in turn be converted to naive hiPSCs. Here, the authors directly reprogram somatic cells to form both naive and primed isogenic hiPSCs and confirm the similarity of naive hiPSCs to their in vivo counterparts.