Publications by authors named "Jenna A Lieberman"
Accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered positive facilitators of transcription. Here, we show that, in contrast to this general assumption, human topoisomerase IIα (TOP2A) activity at promoters represses transcription of immediate early genes such as c-FOS, maintaining them under basal repressed conditions.
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- - The study examined the responses of 20 volunteers who received the Moderna or Pfizer-BioNTech vaccines against SARS-CoV-2 and found that after eight weeks, they had high levels of anti-SARS-CoV-2 antibodies and memory B cells similar to those who recovered from infection.
- - While the vaccines produced potent neutralizing antibodies targeting the virus, their effectiveness against certain variants with mutations (E484K, N501Y, K417N) was notably reduced.
- - The findings indicate that it’s crucial to evaluate the effectiveness of monoclonal antibodies against new variants and suggest that mRNA vaccines may require updates over time to maintain their effectiveness.
Article Synopsis
- Over 100 million people have been infected by SARS-CoV-2, resulting in over two million deaths, prompting the use of mRNA vaccines like Moderna and Pfizer-BioNTech to combat COVID-19.
- A study of 20 volunteers showed that both vaccines produced strong antibody responses and memory B cells, comparable to those seen in individuals recovered from natural infections.
- However, the effectiveness of these vaccine-induced antibodies was slightly reduced against certain SARS-CoV-2 variants, indicating that continuous monitoring and potential updates to vaccines may be necessary to maintain their efficacy.
Topoisomerase 2 (TOP2) DNA transactions proceed via formation of the TOP2 cleavage complex (TOP2cc), a covalent enzyme-DNA reaction intermediate that is vulnerable to trapping by potent anticancer TOP2 drugs. How genotoxic TOP2 DNA-protein cross-links are resolved is unclear. We found that the SUMO (small ubiquitin-related modifier) ligase ZATT (ZNF451) is a multifunctional DNA repair factor that controls cellular responses to TOP2 damage.
View Article and Find Full Text PDFMutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for normal cerebellar development. Genetic inactivation of Chd7 in cerebellar granule neuron progenitors leads to cerebellar hypoplasia in mice, due to the impairment of granule neuron differentiation, induction of apoptosis and abnormal localization of Purkinje cells, which closely recapitulates known clinical features in the cerebella of CHARGE patients.
View Article and Find Full Text PDFAtaxia telangiectasia is caused by mutations in ATM and represents a paradigm for cancer predisposition and neurodegenerative syndromes linked to deficiencies in the DNA-damage response. The role of ATM as a key regulator of signalling following DNA double-strand breaks (DSBs) has been dissected in extraordinary detail, but the impact of this process on DSB repair still remains controversial. Here we develop novel genetic and molecular tools to modify the structure of DSB ends and demonstrate that ATM is indeed required for efficient and accurate DSB repair, preventing cell death and genome instability, but exclusively when the ends are irreversibly blocked.
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