Co-directional (CD) transcription–replication conflicts (TRCs) arise when the DNA replication and transcription machineries progress along the same DNA template. Although generally considered less severe than head-on (HO) TRCs, CD TRCs are now recognized as frequent and actively regulated events that influence genome stability. The Cullin 3–Potassium channel tetramerization domain containing 10 (KCTD10) ubiquitin ligase complex functions as a bivalent sensor that detects CD collisions and directs the nonproteolytic ubiquitination of the elongation factor TCEA2, transiently remodeling RNA polymerase II to permit replisome bypass. This sensing-driven remodeling reframes CD TRCs as dynamic decision nodes where replication and transcription priorities are continuously negotiated, highlighting how conflict geometry, ubiquitin signaling, and genome maintenance are functionally integrated.
