title: RecQL4 is required for the association of Mcm10 and Ctf4 with replication origins in human cells.
abstract: Though RecQL4 was shown to be essential for the initiation of DNA replication in mammalian cells, its role in initiation is poorly understood. Here, we show that RecQL4 is required for the origin binding of Mcm10 and Ctf4, and their physical interactions and association with replication origins are controlled by the concerted action of both CDK and DDK activities. Although RecQL4-dependent binding of Mcm10 and Ctf4 to chromatin can occur in the absence of pre-replicative complex, their association with replication origins requires the presence of the pre-replicative complex and CDK and DDK activities. Their association with replication origins and physical interactions are also targets of the DNA damage checkpoint pathways which prevent initiation of DNA replication at replication origins. Taken together, the RecQL4-dependent association of Mcm10 and Ctf4 with replication origins appears to be the first important step controlled by S phase promoting kinases and checkpoint pathways for the initiation of DNA replication in human cells.
authors.affiliation: a Department of Biology Education; Seoul National University ; Seoul , Korea.
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Im
authors.forename: Soon-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Cho
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Bae
authors.forename: Jerard
authors.initials: J
authors.lastname: Hurwitz
authors.forename: Joon-Kyu
authors.initials: JK
authors.lastname: Lee
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D053484:RecQ Helicases / Q000502:physiology*; D018741:Replication Origin
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C489613:MCM10 protein, human; C544202:WDHD1 protein, human; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C506731:RECQL4 protein, human; D064110:Minichromosome Maintenance Proteins; D053484:RecQ Helicases
keywords: BiFC, bimolecular fluorescence complementation; CDK; CDK, cyclin dependent kinase; ChIP, chromatin immunoprecipitation; Ctf4/And-1; DDK; DDK, Dbf4 dependent kinase; DNA replication; Mcm10; RecQL4; cell cycle; checkpoint; pre-RC, pre-replicative complex