biostudies-literatureCho WHPHS HHSNIGMS NIH HHS2523-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC3574903biostudies-literatureUnknown110(7)Tim (Timeless) and Tipin (Tim-interacting protein) form a stable heterodimeric complex that influences checkpoint responses and replication fork progression. We report that the Tim-Tipin complex interacts with essential replication fork proteins and affects their biochemical properties. The Tim-Tipin complex, reconstituted and purified using the baculovirus expression system, interacts directly with Mcm complexes and inhibits the single-stranded DNA-dependent ATPase activities of the Mcm2-7 and Mcm4/6/7 complexes, the DNA unwinding activity of the Mcm4/6/7 complex, and the DNA unwinding and ATPase activity of Cdc45-Mcm2-7-GINS complex, the presumed replicative DNA helicase in eukaryotes. Although stable interactions between Tim-Tipin and DNA polymerases (pols) were not observed in immunoprProceedings of the National Academy of Sciences of the United States of AmericaHuman Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.PMC3574903R01 GM034559GMS R01 GM034559Tappin IAn YYCho WHKang YHLee JKHurwitz JfalseHuman Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.Tim (Timeless) and Tipin (Tim-interacting protein) form a stable heterodimeric complex that influences checkpoint responses and replication fork progression. We report that the Tim-Tipin complex interacts with essential replication fork proteins and affects their biochemical properties. The Tim-Tipin complex, reconstituted and purified using the baculovirus expression system, interacts directly with Mcm complexes and inhibits the single-stranded DNA-dependent ATPase activities of the Mcm2-7 and Mcm4/6/7 complexes, the DNA unwinding activity of the Mcm4/6/7 complex, and the DNA unwinding and ATPase activity of Cdc45-Mcm2-7-GINS complex, the presumed replicative DNA helicase in eukaryotes. Although stable interactions between Tim-Tipin and DNA polymerases (pols) were not observed in immunopr2013-01-01T00:00:00Z2013 Feb2025-04-26T08:55:04.156Z2019-03-27T01:04:54ZS-EPMC35749032335967610.1073/pnas.1222494110