title: Coordinated protein and DNA remodeling by human HLTF on stalled replication fork.
abstract: Human helicase-like transcription factor (HLTF) exhibits ubiquitin ligase activity for proliferating cell nuclear antigen (PCNA) polyubiquitylation as well as double-stranded DNA translocase activity for remodeling stalled replication fork by fork reversal, which can support damage bypass by template switching. However, a stalled replication fork is surrounded by various DNA-binding proteins which can inhibit the access of damage bypass players, and it is unknown how these proteins become displaced. Here we reveal that HLTF has an ATP hydrolysis-dependent protein remodeling activity, by which it can remove proteins bound to the replication fork. Moreover, we demonstrate that HLTF can displace a broad spectrum of proteins such as replication protein A (RPA), PCNA, and replication factor C (RFC), thereby providing the first example for a protein clearing activity at the stalled replication fork. Our findings clarify how remodeling of a stalled replication fork can occur if it is engaged in interactions with masses of proteins.
authors.affiliation: Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvari krt.62, H-6726, Szeged, Hungary.
authors.forename: Yathish Jagadheesh
authors.initials: YJ
authors.lastname: Achar
authors.forename: David
authors.initials: D
authors.lastname: Balogh
authors.forename: Lajos
authors.initials: L
authors.lastname: Haracska
mesh_terms: D004247:DNA / Q000378:metabolism*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051716:Replication Protein A / Q000378:metabolism; D051818:Replication Protein C / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C100023:HLTF protein, human; D018809:Proliferating Cell Nuclear Antigen; D051716:Replication Protein A; D014157:Transcription Factors; D004247:DNA; D051818:Replication Protein C