title: Noncanonical role of the 9-1-1 clamp in the error-free DNA damage tolerance pathway.
abstract: Damaged DNA is an obstacle during DNA replication and a cause of genome instability and cancer. To bypass this problem, eukaryotes activate DNA damage tolerance (DDT) pathways that involve ubiquitylation of the DNA polymerase clamp proliferating cell nuclear antigen (PCNA). Monoubiquitylation of PCNA mediates an error-prone pathway by recruiting translesion polymerases, whereas polyubiquitylation activates an error-free pathway that utilizes undamaged sister chromatids as templates. The error-free pathway involves recombination-related mechanisms; however, the factors that act along with polyubiquitylated PCNA remain largely unknown. Here we report that the PCNA-related 9-1-1 complex, which is typically linked to checkpoint signaling, participates together with Exo1 nuclease in error-free DDT. Notably, 9-1-1 promotes template switching in a manner that is distinct from its canonical checkpoint functions and uncoupled from the replication fork. Our findings thus reveal unexpected cooperation in the error-free pathway between the two related clamps and indicate that 9-1-1 plays a broader role in the DNA damage response than previously assumed.
authors.affiliation: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Georgios Ioannis
authors.initials: GI
authors.lastname: Karras
authors.forename: Marco
authors.initials: M
authors.lastname: Fumasoni
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Sienski
authors.forename: Fabio
authors.initials: F
authors.lastname: Vanoli
authors.forename: Dana
authors.initials: D
authors.lastname: Branzei
authors.forename: Stefan
authors.initials: S
authors.lastname: Jentsch
mesh_terms: D004249:DNA Damage; D005090:Exodeoxyribonucleases / Q000378:metabolism; D016195:G2 Phase; D005820:Genetic Testing; D008938:Mitosis; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013698:Templates, Genetic
chemical_list: D046912:Multiprotein Complexes; D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I