LEO1 is a partner for Cockayne syndrome protein B (CSB) in response to transcription-blocking DNA damage

Abstract Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as interacting protein partner of full-length C-terminal (Pro1010-Cys1493) two independent screens. member the RNA polymerase associated factor 1 complex (PAF1C) with roles transcription elongation chromatin modification. Supportive Y2H results, purified, recombinant directly interact vitro, proteins exist common within human cells. In addition, fluorescently tagged are both recruited localized DNA damage sites Cell fractionation experiments revealed transcription-dependent, coordinated association following either UVC irradiation or cisplatin treatment HEK293T cells, whereas response menadione was distinct, suggesting that this collaboration occurs mainly context bulky transcription-blocking lesions. Consistent interaction repair, knockdown knockout resulted reduced recruitment chromatin, increased sensitivity light damage, synthesis recovery slower excision cyclobutane pyrimidine dimers irradiation; absence diminished recruitment. Our data indicate reciprocal communication between transcription-associated repair recovery.