DNA repair and antibody diversification: the 53BP1 paradigm. 2023

Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
Laboratory of Genome Diversification and Integrity, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany. Electronic address: eleni.kabrani@mdc-berlin.de.

The DNA double-strand break (DSB) repair factor 53BP1 has long been implicated in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, the dissection of the underlying molecular activities is hampered by a paucity of studies [V(D)J] and plurality of phenotypes (CSR) associated with 53BP1 deficiency. Here, we revisit the currently accepted roles of 53BP1 in antibody diversification in view of the recent identification of its downstream effectors in DSB protection and latest advances in genome architecture. We propose that, in addition to end protection, 53BP1-mediated end-tethering stabilization is essential for CSR. Furthermore, we support a pre-DSB role during V(D)J recombination. Our perspective underscores the importance of evaluating repair of DSBs in relation to their dynamic architectural contexts.

UI MeSH Term Description Entries
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008322 Mammals Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young. Mammalia,Mammal
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071857 Tumor Suppressor p53-Binding Protein 1 A nuclear and cytoplasmic protein that associates with KINETOCHORES and contains a C-terminal TUDOR DOMAIN. It plays a critical role in the cellular response to DNA DAMAGE and localizes to DOUBLE-STRAND DNA BREAKS. It may also function in M PHASE CELL CYCLE CHECKPOINTS and as an enhancer of TUMOR SUPPRESSOR PROTEIN P53-mediated transcriptional activation. 53BP1 Protein,TP53BP1 Protein,Tumor Protein p53-Binding Protein, 1,p202 Protein,Tumor Protein p53 Binding Protein, 1,Tumor Suppressor p53 Binding Protein 1
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000906 Antibodies Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
D017578 Immunoglobulin Class Switching Gene rearrangement of the B-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing. Class Switching,Ig Class Switching,Isotype Switching,Class Switching, Ig,Class Switching, Immunoglobulin,Class Switchings,Class Switchings, Ig,Class Switchings, Immunoglobulin,Ig Class Switchings,Immunoglobulin Class Switchings,Isotype Switchings,Switching, Class,Switching, Ig Class,Switching, Immunoglobulin Class,Switching, Isotype,Switchings, Class,Switchings, Ig Class,Switchings, Immunoglobulin Class,Switchings, Isotype
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053903 DNA Breaks, Double-Stranded Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently. Double-Stranded DNA Breaks,Double-Strand DNA Breaks,Double-Stranded DNA Break,Break, Double-Strand DNA,Break, Double-Stranded DNA,Breaks, Double-Strand DNA,Breaks, Double-Stranded DNA,DNA Break, Double-Strand,DNA Break, Double-Stranded,DNA Breaks, Double Stranded,DNA Breaks, Double-Strand,Double Strand DNA Breaks,Double Stranded DNA Break,Double Stranded DNA Breaks,Double-Strand DNA Break

Related Publications

Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
November 2007, DNA repair,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
December 2021, Nature,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
February 2014, Trends in cell biology,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
February 2016, DNA repair,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
August 2018, Nature,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
December 2019, Nature structural & molecular biology,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
August 2002, Nature reviews. Immunology,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
August 2019, The EMBO journal,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
August 2016, Nature structural & molecular biology,
Eleni Kabrani, and Tannishtha Saha, and Michela Di Virgilio
February 2019, The Journal of cell biology,
Copied contents to your clipboard!