Fused in sarcoma regulates DNA replication timing and kinetics
Weiyan Jia, Sang Hwa Kim, Mark Scalf, Peter Tonzi, Robert J. Millikin, William M. Guns, Lu Liu, Adam S. Mastrocola, Lloyd M. Smith, Tony T. Huang, Randal S. Tibbetts
Abstract
cells also exhibited reduced proliferative potential that correlated with reduced speed of replication fork progression, diminished loading of prereplication complexes, enhanced micronucleus formation, and attenuated expression and splicing of S-phase-associated genes. Finally, FUS-deficient cells exhibited genome-wide alterations in DNA replication timing that were reversed upon re-expression of FUS complementary DNA. We also showed that FUS-dependent replication domains were enriched in transcriptionally active chromatin and that FUS was required for the timely replication of transcriptionally active DNA. These findings suggest that alterations in DNA replication kinetics and programming contribute to genome instability and functional defects in FUS-deficient cells.