Targeting RLF and RLF-MYCL Fusion: A Novel Regulator of Replication Fork Speed and Cancer Epigenetics
Accurate DNA replication is essential for genome integrity, and disruptions in replication fork dynamics contribute to developmental disorders and cancer. This project focuses on the Rearranged L-myc Fusion (RLF) gene, a newly identified regulator of replication fork speed and chromatin architecture. RLF is a zinc-finger transcription factor involved in epigenetic regulation and replication factory organisation. Its fusion with MYCL (RLF-MYCL) in certain cancers suggests a gain-of-function mechanism that drives oncogenesis and disrupts genome stability.
We aim to unravel how RLF and RLF-MYCL fusion regulate DNA replication, cohesin positioning, and 3D genome organisation using innovative tools including DNAscent, a world-first replication mapping assay based on nanopore sequencing, and genome-wide ChIP-seq and Hi-C. This research will provide foundational insights into the role of RLF in normal and cancer cells and guide the development of targeted therapeutics.