Biology subjects

Oyeniran, C.

Publications and source records attributed to Oyeniran, C..

2 recordsLinked to original sources

bioRxiv2024

Promoter- and Enhancer-Dependent Cohesin Loading Initiates Chromosome Looping to Fold Tcrb Loci for Long-Range Recombination

Cohesin-mediated chromosome looping regulates diverse processes, including antigen receptor (AgR) gene assembly by V(D)J recombination. To understand mechanisms that coordinate genome topologies, we focused on a genetically tractable AgR locus, Tcrb. Cohesin loading and initiating loop extrusion (LE) from a nearby CTCF-binding element (CBE) required the promoter of the most 5V{beta} segment, creating long-range contacts with target downstream DJ{beta} segments within the recombination center (RC). CBEs flanking the RC have multiple functions: terminators of LE originating in the V{beta} cluster, initiators of LE in the RC, and insulation of enhancer activity. Deletion of the Tcrb super-enhancer abolished loop extrusion from the neighboring RC but spared long-range contacts, indicating that unidirectional loop extrusion from upstream V{beta} segments was sufficient. Thus, V{beta} promoter- or enhancer-dependent cohesin loading initiates LE in opposite directions across the locus to assemble a broad Tcrb repertoire, a finding that has broad implications for genomic architecture and function.

molecular biology↗

bioRxiv2020

Aberrant RNA methylation triggers recruitment of an alkylation repair complex

A critical question in genome stability is the nature of the chemical damage responsible for repair activation. We previously reported a novel pathway specifically activated during alkylation damage in human cells, where the E3 ubiquitin ligase RNF113A mediates the recruitment of the ASCC repair complex. Yet the mechanistic basis for the alkylation damage selectivity of this pathway remains unclear. Here, we demonstrate that RNA but not DNA alkylation is the initiating signal for this process. Aberrantly methylated RNA is sufficient to recruit ASCC, while an RNA dealkylase suppresses ASCC recruitment during chemical alkylation. This aberrant RNA methylation causes transcriptional repression in a manner dependent on the ASCC complex. We show that an alkylated pre-mRNA, or an RNA containing a single damaged base, is sufficient to activate RNF113A E3 activity in a phosphorylation-dependent manner. Together, our work identifies an unexpected role for RNA damage in eliciting a DNA repair response, and suggests that RNA may serve as the "canary in the coal mine" for sensing alkylation damage.

molecular biology↗