Dimerization of FIR upon FUSE DNA binding suggests a mechanism of c-myc inhibition

c-myc is essential for cell homeostasis and growth but lethal if improperly regulated. Transcription of this oncogene is governed by the counterbalancing forces of two proteins on TFIIH—the FUSE binding protein (FBP) and the FBP-interacting repressor (FIR). FBP and FIR recognize single-stranded DNA upstream of the P1 promoter, known as FUSE, and influence transcription by oppositely regulating TFIIH at the promoter site. Size exclusion chromatography coupled with light scattering reveals that an FIR dimer binds one molecule of single-stranded DNA. The crystal structure confirms that FIR binds FUSE as a dimer, and only the N-terminal RRM domain participates in nucleic acid recognition. Site-directed mutations of conserved residues in the first RRM domain reduce FIR's affinity for FUSE, while analogous mutations in the second RRM domain either destabilize the protein or have no effect on DNA binding. Oppositely oriented DNA on parallel binding sites of the FIR dimer results in spooling of a single strand of bound DNA, and suggests a mechanism for c-myc transcriptional control

The Effectiveness of Ketamine in Pediatric Acute Deafferentation Pain after Spinal Cord Injury

Deafferentation pain and allodynia commonly occur after spinal cord trauma, but its treatment is often challenging. The literature on effective therapies for pediatric deafferentation pain, especially in the setting of spinal cord injury, is scarce. We report the case of a 12-year-old patient with acute allodynia after a gunshot injury to the spine. The pain was refractory to multiple analgesics, but resolved with ketamine, which also improved the patient’s physical function and quality of life, a trend that continued many months after the injury. We suggest that early initiation of ketamine may be effective for acute pediatric deafferentation pain secondary to spinal cord injury, as well as preventing chronic pain states in that population