title: The Slx4-Dpb11 scaffold complex: coordinating the response to replication fork stalling in S-phase and the subsequent mitosis.
abstract: Replication fork stalling at DNA lesions is a common problem during the process of DNA replication. One way to allow the bypass of these lesions is via specific recombination-based mechanisms that involve switching of the replication template to the sister chromatid. Inherent to these mechanisms is the formation of DNA joint molecules (JMs) between sister chromatids. Such JMs need to be disentangled before chromatid separation in mitosis and the activity of JM resolution enzymes, which is under stringent cell cycle control, is therefore up-regulated in mitosis. An additional layer of control is facilitated by scaffold proteins. In budding yeast, specifically during mitosis, Slx4 and Dpb11 form a cell cycle kinase-dependent complex with the Mus81-Mms4 structure-selective endonuclease, which allows efficient JM resolution by Mus81. Furthermore, Slx4 and Dpb11 interact even prior to joining Mus81 and respond to replication fork stalling in S-phase. This S-phase complex is involved in the regulation of the DNA damage checkpoint as well as in early steps of template switch recombination. Similar interactions and regulatory principles are found in human cells suggesting that Slx4 and Dpb11 may have an evolutionary conserved role organizing the cellular response to replication fork stalling.
authors.affiliation: a Max-Planck Institute of Biochemistry ; DNA Replication and Genome Integrity ; Martinsried , Germany.
authors.forename: Lissa N
authors.initials: LN
authors.lastname: Princz
authors.forename: Dalia
authors.initials: D
authors.lastname: Gritenaite
authors.forename: Boris
authors.initials: B
authors.lastname: Pfander
mesh_terms: D059447:Cell Cycle Checkpoints / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D015530:Nuclear Matrix / Q000502:physiology; D016196:S Phase / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D004718:Saccharomycetales
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C097185:DPB11 protein, S cerevisiae; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D004706:Endodeoxyribonucleases; C505436:SLX4 protein, S cerevisiae
keywords: DNA damage response; cell cycle; homologous recombination; joint molecule resolution; post-replicative repair