Class switch recombination (CSR), similar to V(D)J recombination, is thought to involve DNA double strand breaks and repair by the nonhomologous end-joining pathway. A key component of this pathway is DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and a DNA-binding heterodimer (Ku70/80). To test whether DNA-PKcs activity is essential for CSR, we examined whether IgM(+) B cells from scid mice with site-directed H and L chain transgenes were able to undergo CSR. Although B cells from these mice were shown to lack DNA-PKcs activity, they were able to switch from IgM to IgG or IgA with close to the same efficiency as B cells from control transgenic and nontransgenic scid/+ mice, heterozygous for the scid mutation. We conclude that CSR, unlike V(D)J recombination, can readily occur in the absence of DNA-PKcs activity. We suggest nonhomologous end joining may not be the (primary or only) mechanism used to repair DNA breaks during CSR.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194268 | PMC |
| http://dx.doi.org/10.1084/jem.20001871 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The interplay of DNA repair context with target sequence predictably biases Cas9-generated mutations.
Nat Commun
November 2024
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Article Synopsis
- The study investigates how the surrounding DNA sequence affects the repair of double-stranded breaks caused by CRISPR/Cas9, using various genetically modified mouse embryonic stem cell lines.
- Researchers analyzed over 236,000 mutation outcomes from 2800 synthetic DNA sequences, discovering specific roles of DNA repair proteins like Prkdc and Polm in generating small insertions and deletions.
- They developed predictive models for these mutational outcomes based on their findings, enhancing the understanding of DNA repair mechanisms and enabling more accurate control of CRISPR-induced mutations.
Making PI3K superfamily enzymes run faster.
Adv Biol Regul
November 2024
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address:
Article Synopsis
- The phosphoinositide 3-kinase (PI3K) superfamily consists of lipid kinases and PI3K-like protein kinases that share a conserved C-terminal kinase domain, characterized by low basal activity that can be significantly enhanced by various regulatory factors.
- Activators induce conformational changes in the kinase domain that improve ATP-binding and catalysis efficiency, specifically through realignment of the active site and changes in a region known as the PIKK regulatory domain.
- A recent discovery of a small-molecule activator for PI3Kα may lead to the development of specific PI3K activators, with potential applications in wound healing, neurodegeneration treatment, and anti-stroke therapies.
NU7441, a selective inhibitor of DNA-PKcs, alleviates intracerebral hemorrhage injury with suppression of ferroptosis in brain.
PeerJ
November 2024
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Neuronal apoptosis, oxidative stress, and ferroptosis play a crucial role in the progression of secondary brain injury following intracerebral hemorrhage (ICH). Although studies have highlighted the important functions of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in various experimental models, its precise role and mechanism in ICH remain unclear. In this study, we investigated the effects of DNA-PKcs on N2A cells under a hemin-induced hemorrhagic state and a rat model of collagenase-induced ICH .
View Article and Find Full Text PDFPARylation of GCN5 by PARP1 mediates its recruitment to DSBs and facilitates both HR and NHEJ Repair.
Cell Mol Life Sci
November 2024
Shilpee Dutt Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, 410210, India.
Efficient DNA double strand break (DSB) repair is necessary for genomic stability and determines efficacy of DNA damaging cancer therapeutics. Spatiotemporal dynamics and post-translational modifications of repair proteins at DSBs dictate repair efficacy. Here, we identified a non-canonical function of GCN5 in regulating both HR and NHEJ repair post genotoxic stress.
View Article and Find Full Text PDFNuclear porcupine mediates XRCC6/Ku70 S-palmitoylation in the DNA damage response.
Exp Hematol Oncol
November 2024
Department of Biochemistry and Molecular Biology, The Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
Background: The activation of the DNA damage response (DDR) heavily relies on post-translational modifications (PTMs) of proteins, which play a crucial role in the prevention of genetic instability and tumorigenesis. Among these PTMs, palmitoylation is a highly conserved process that is dysregulated in numerous cancer types. However, its direct involvement in the DDR and the underlying mechanisms remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!