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Jan 16, 2020

RPG Seminar Series (Speaker: Miss LI Junshi / Miss ZHENG Zhengfan)

Date: Thursday, 16 January 2020

Venue: Seminar Room 7, LG/F
Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Time: 5:00 p.m.


Title: DYRK1A Promotes DSB Repair by Regulating Local Transcriptional Activities
Speaker: Miss LI Junshi (PhD candidate)

Summary:
Being considered as the most cytotoxic lesions, DNA double-strand breaks (DSBs) on active chromatin not only compromise genome stability and contribute to tumorigenesis, but also alter transcriptome signatures and perturb cell functions. While cells have evolved strategies to orchestrate DSB repair on transcribing chromatin, mechanistically how this is coupled to transcription pausing and resumption remains obscure. Here we have identified DYRK1A as a novel determinant that promotes DSB repair by controlling local transcription activities. While DYRK1A loss leads to DSB repair defects, such deficiency can be alleviated by pre-treatment with transcription inhibitors, suggesting DYRK1A fosters DSB repair through transcription-associated mechanisms. Consistent with this speculation, DYRK1A ablation results in prolonged accumulation of the key negative transcription regulator, NELF-E, at DSBs. This coincides with the delayed transcription recovery during DSB repair in DYRK1A-inactivated cells. Taken together, our study suggests that DYRK1A facilitates DSB repair by regulating transcription in cis to DSBs.


Title: Elucidating the role of PHF5A in the establishment and maintenance of multipotent neural crest stem cells
Speaker: Miss ZHENG Zhengfan (PhD candidate)

Summary:
In vertebrates, neural crest cells (NCCs) belong to a migratory population of multipotent stem cells which arise at the neural plate border. Functional studies showed that the NC specifier genes, Sox9, FoxD3 and Snail2, determine NCC fate and their expressions are regulated by neural plate border specifiers. However, it remains unclear how these NC specifiers genes are regulated at the transcriptional and post-transcriptional levels. Our mass spectrometry analysis identified PHF5A which has been shown to regulate gene transcription and splicing. By in ovo electroporation, we found that overexpression, morpholino- and CRISPR/Cas9-targeted PHF5A downregulated the expression of NC specifier genes, suggesting that appropriate level of PHF5A expression is crucial for the establishment of NCC fate. Thus, we hypothesize that genetic manipulation of PHF5A expression might disrupt the integrity of the endogenous transcriptional machinery complex and/or splicing events that are required for the initiation and/or maintenance of NC specifier genes expression.

 

ALL ARE WELCOME