Structural basis for the initiation of eukaryotic transcription-coupled DNA repair

Eukaryotic transcription-coupled repair (TCR) is an important and well-conserved sub-pathway of nucleotide excision repair that preferentially removes DNA lesions from the template strand that block translocation of RNA polymerase II (Pol II). Cockayne syndrome group B (CSB, also known as ERCC6) protein in humans (or its yeast orthologues, Rad26 in Saccharomyces cerevisiae and Rhp26 in Schizosaccharomyces pombe) is among the first proteins to be recruited to the lesion-arrested Pol II during the initiation of eukaryotic TCR. Mutations in CSB are associated with the autosomal-recessive neurological disorder Cockayne syndrome, which is characterized by progeriod features, growth failure and photosensitivity1. The molecular mechanism of eukaryotic TCR initiation remains unclear, with several long-standing unanswered questions. How cells distinguish DNA lesion-arrested Pol II from other forms of arrested Pol II, the role of CSB in TCR initiation, and how CSB interacts with the arrested Pol II complex are all unknown. The lack of structures of CSB or the Pol II–CSB complex has hindered our ability to address these questions. Here we report the structure of the S. cerevisiae Pol II–Rad26 complex solved by cryo-electron microscopy. The structure reveals that Rad26 binds to the DNA upstream of Pol II, where it markedly alters its path. Our structural and functional data suggest that the conserved Swi2/Snf2-family core ATPase domain promotes the forward movement of Pol II, and elucidate key roles for Rad26 in both TCR and transcription elongation

Simultaneous ossification of the posterior longitudinal ligament and ossification of the ligamentum flavum causing upper thoracic myelopathy in DISH: case report and literature review

A rare case of a 44-year-old Chinese male with diffuse idiopathic skeletal hyperostosis (DISH) and simultaneous ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) at T1–2 causing thoracic myelopathy is reported herein. Posterior decompression without extirpating the OPLL was performed at T1–2. Postoperatively, symptoms were greatly improved, with remaining hyperreflexia and Grade 4/5 muscle strength in the lower extremities. The Japanese Orthopedic Association score improved from 5 preoperatively to 9 at final follow-up. The presence of a cyst due to leakage of cerebrospinal fluid was confirmed by MRI at day 27, but it resolved after conservative management. The clinical manifestation of DISH, the relationship among DISH, OPLL, and OLF, and management of thoracic myelopathy due to OPLL and OLF were reviewed