53BP1 is required for class switch recombination

Ward, Irene M.; Reina‐San‐Martin, Bernardo; Olaru, Alexandru; Minn, Kay; Tamada, Koji; Lau, Julie S.; Cascalho, Marília; Chen, Lieping; Nussenzweig, André; Livák, Ferenc; Nussenzweig, Michel C.; Chen, Junjie

doi:10.1083/jcb.200403021

Cited by 298 publications

(339 citation statements)

References 38 publications

(52 reference statements)

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“…These results suggest that, whereas CtIP promotes nucleolytic processing of DSBs in all cell cycle phases, other factors that stimulate or antagonize the extension of resected tracks may be distinct and regulated in a cell cycle-dependent manner. , CtIP +/2 , 53BP1 2/2 (Ward et al, 2004), BRCA1 f(11)/f(11) (here reported BRCA111 f/f ; NCI mouse repository), Ku80 2/2 (Nussenzweig et al, 1996), CD19 Cre (Rickert et al, 1997), EXO1 2/2 (Wei et al, 2003), and ROSA26-STOP-EYFP (Srinivas et al, 2001) mice have been described. BAC RP11-104H10 containing human CtIP genomic sequence was used to generate transgenic mice.…”

Section: Phosphorylation Of Ctip At T847 Is Essential For Genome Stabmentioning

confidence: 99%

CtIP-mediated resection is essential for viability and can operate independently of BRCA1

Polato¹,

Bunting²,

Wong³

et al. 2014

J Cell Biol

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Section: Phosphorylation Of Ctip At T847 Is Essential For Genome Stabmentioning

confidence: 99%

CtIP-mediated resection is essential for viability and can operate independently of BRCA1

Polato¹,

Bunting²,

Wong³

et al. 2014

J Cell Biol

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“…As eluded to in the introduction, experimental evidence has demonstrated that CSR, like V(D)J recombination, involves the generation of DNA dsb: (1) an episomal circle is generated during CSR (Chaudhuri and Alt, 2004); (2) AID-dependent DNA dsb have been detected by ligated mediated PCR assays in Switch regions of mitogen-activated B cells (Wuerffel et al, 1997;Catalan et al, 2003;Rush et al, 2004); (3) phosphorylation of histone H2AX (gH2AX), which spreads around DNA dsb, is detected at the IgH locus in an AID-dependent manner, in B cells activated for CSR (Petersen et al, 2001); (4) CSR is impaired in mice deficient for H2AX, ATM, p53 binding protein 1 and Nbs1, which are DDR early components (Reina-San-Martin et al, 2003, 2004Lumsden et al, 2004;Manis et al, 2004;Ward et al, 2004;Kracker et al, 2005). The link between AIDdriven DNA cytidine deamination and the introduction of DNA dsb in Ig S regions is not fully established yet.…”

Section: Nhej and Csrmentioning

confidence: 99%

V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining

et al. 2007

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The immune system is the site of intense DNA damage/ modification, which occur during the development and maturation of B and T lymphocytes. V(D)J recombination is initiated by the Rag1 and Rag2 proteins and the formation of a DNA double-strand break (DNA dsb). This DNA lesion is repaired through the use of the nonhomologous end-joining (NHEJ) pathway, several factors of which have been identified through the survey of immunodeficient conditions in humans and mice. Upon antigenic recognition in secondary lymphoid organs, mature B cells further diversify their repertoire through class switch recombination (CSR). CSR is a region-specific rearrangement process triggered by the activation-induced cytidine deaminase factor and also proceeds through the introduction of DNA dsb. However, unlike V(D)J recombination, CSR does not rely strictly on NHEJ for the repair of the DNA lesion. Instead, CSR, but not V(D)J recombination, requires the major factors of the DNA damage response. V(D)J recombination and CSR thus represent an interesting paradigm to study the regulation among the various DNA repair pathways. Oncogene (2007) 26, 7780-7791; doi:10.1038/sj.onc.1210875 Keywords: V(D)J recombination; class switch recombination; SCID; Artemis; Cernunnos; NHEJ V(D)J recombination and CSR: two rearrangement processes that shape the immune system repertoire B and T lymphocytes respond to foreign pathogens through specialized antigenic receptors, the B-cell receptor and T-cell receptor, respectively. The required diversity of these receptors is ensured by the V(D)J recombination process (Figure 1) which assembles previously scattered Variable (V), Diversity (D) and Joining (J) encoding gene segments through a specialized somatic DNA rearrangement mechanism (Tonegawa, 1983). The reaction is initiated by the lymphoid-specific factors, Rag1 and Rag2, which recognize recombination signal sequences (RSS) that flank all V, D and J gene units and introduce a DNA dsb at the border of the RSS (see Dudley et al. (2005) for a review on V(D)J recombination). The resulting DNA double-strand break (DNA dsb) is resolved by the ubiquitous DNA repair machinery known as non-homologous end-joining (NHEJ). The convergent efforts of scientists in the immunology and DNA repair fields were decisive in defining the various actors and molecular mechanisms of this DNA repair pathway over the years as will be discussed below.The terminal maturation of B lymphocytes, which occurs in germinal centres of secondary lymphoid organs upon antigen recognition, is accompanied by two additional molecular processing of immunoglobulin genes that increase the efficiency of the humoral response: (1) the class switch recombination (CSR, Figure 2) exchanges the immunoglobulin (Ig) constant region (CH), thus modifying the function of the Ig without altering its antigenic specificity (Manis et al., 2002b) and (2) somatic hypermutations are introduced in the Ig variable domains, thus increasing their affinity for antigen (Papavasiliou and Schatz, 2002). These two events ar...

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“…Cells lacking 53BP1 are sensitive to DNA damaging agents and have defects in both S-phase and G2M checkpoints (most noticeable after low but not high doses of ionizing radiation) (Fernandez-Capetillo et al, 2002;Mochan et al, 2003). 53BP1 function is also required for class-switch recombination and has been implicated in NHEJ in a non-classical V(D)J recombination pathway (Ward et al, 2004;Xie et al, 2007;Difilippantonio et al, 2008). Overexpression of a dominantnegative 53BP1 construct suppressed NHEJ and increased frequency of HR-mediated repair, suggesting 53BP1 is involved in regulating the choice between NHEJ and HR-mediated repair of DNA DSBs (Xie et al, 2007).…”

Section: Bp1 and Brca1: Synthetic Viabilitymentioning

confidence: 99%

BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability

Aly¹,

Ganesan²

2011

Journal of Molecular Cell Biology

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BRCA1 plays a critical role in the regulation of homologous recombination (HR)-mediated DNA double-strand break repair. BRCA1-deficient cancers have evolved to tolerate loss of BRCA1 function. This renders them vulnerable to agents, such as PARP inhibitors, that are conditionally 'synthetic lethal' with their underlying repair defect. Recent studies demonstrate that BRCA1-deficient cells may acquire resistance to these agents by partially correcting their defect in HR-mediated repair, either through reversion mutations in BRCA1 or through 'synthetic viable' loss of 53BP1. These findings and their clinical implications will be reviewed in this article.

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53BP1 is required for class switch recombination

Cited by 298 publications

References 38 publications

CtIP-mediated resection is essential for viability and can operate independently of BRCA1

CtIP-mediated resection is essential for viability and can operate independently of BRCA1

V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining

BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability

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