Biology subjects

Wong, T.-F.

Publications and source records attributed to Wong, T.-F..

2 recordsLinked to original sources

bioRxiv2026

Mechanistic insights into chromatin modulation by the orphan remodeler ATRX

Alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) is an ATP-dependent chromatin remodeler that performs diverse functions, including spacing nucleosomes, facilitating the deposition of histone variant H3.3, and preventing replication stress. The mechanism by which ATRX modulates chromatin is unknown. Here, our cryo-EM structure revealed that ATRX recognizes and modulates the nucleosome through its C-terminal regions by embracing and unwrapping [~]18 base-pair nucleosomal DNA near the entry/exit sites in the presence of ADP*BeF3. Strikingly, the DNA minor groove between SHL6 and SHL7 is profoundly deformed by a "pin-like" structure in ATRX, which uniquely intercalates the aromatic side chain of a phenylalanine into the base stackings. Biochemical assays revealed the crucial role of this phenylalanine in sliding the nucleosome without affecting the ATPase activity. Such a "pin-like" structure mimics a "foot-step" on the DNA ladder, which differentiates ATRX from other remodelers. To translocate the DNA on the nucleosome, two more features, including a disordered insertion that contacts the histone surface and a positively charged loop bridging the cross-gyre interactions, serve as essential anchors for the nucleosome modulation by ATRX. Together, we propose a "climbing" model for how ATRX mobilizes the DNA upon ATP hydrolysis.

biochemistry↗

bioRxiv2022

Thermococci-to-Clostridia Pathway for the Evolution of the Bacteria Domain

With the identification of an archaeal Last Universal Common Ancestor phylogenetically related to Methanopyrus, the origin of Bacteria becomes a choice between independent emergence versus descent from Archaea. Recently, use of the similarity between paralogous valyl-tRNA synthetase (VARS) and isoleucyl-tRNA synthetase (IARS) as a measure of the ages of bacteria indicated that an Ancestral Bacterial Cluster centred at clostridial Mahella australiensis (Mau) were the oldest bacteria. Clostridial Thermincola potens (Tpo) also displayed an elevated similarity VARS-IARS bitscore. Overall, the high-bitscore bacteria dominated by Clostridia comprised a number of hydrogen producers. A search for archaea capable of hydrogen production that might be ancestral to the Bacteria domain yielded candidates led by Thermococci which, like Clostridia, form hydrogen through dark fermentation. A two-domain VARS tree based on Mahella, Thermincola, a broad spectrum of archaea together with both well known and newly reported species of Thermococci allocated these two Clostridia to a minor-Thermococcal division on the tree. The kinship between Thermoccoci and Clostridia suggested by this allocation was substantiated by conserved oligopeptide segments on their VARS sequences. It was therefore suggested that a Thermococci-to-Clostridia evolutionary pathway brought about the emergence of the Bacteria domain.

genomics↗