SMC5/6 acts jointly with Fanconi anemia factors to support DNA repair and genome stability

ABSTRACT: SMC5/6 function in genome integrity remains elusive. Here we show that SMC5 dysfunction in avian DT40 B cells causes mitotic delay and hypersensitivity towards DNA intra- and inter-strand crosslinkers (ICLs), with smc5 mutants being epistatic to FANCC and FANCM mutations affecting the Fanconi anemia (FA) pathway. Mutations in the checkpoint clamp loader RAD17 and the DNA helicase DDX11, acting in an FA-like pathway, do not aggravate the damage sensitivity caused by SMC5 dysfunction in DT40 cells. SMC5/6 knockdown in HeLa cells causes MMC sensitivity, increases nuclear bridges, micronuclei and mitotic catastrophes in a manner similar and epistatic to FANCD2 knockdown. In both DT40 and HeLa systems, SMC5/6 deficiency increases FANCD2 ubiquitylation and, unlike FANCD2 depletion, RAD51 focus f

SUBMITTER: Dr. Francesco Rossi 

PROVIDER: S-SCDT-EMBOR-2019-48222V1 | biostudies-other |

REPOSITORIES: biostudies-other