Activation of the FA pathway mediated by phosphorylation and ubiquitination

Masamichi Ishiai, Koichi Sato, Junya Tomida, Hiroyuki Kitao, Hitoshi Kurumizaka, Minoru Takata

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Fanconi anemia (FA) is a devastating hereditary condition that impacts genome integrity, leading to clinical features such as skeletal and visceral organ malformations, attrition of bone marrow stem cells, and carcinogenesis. At least 21 proteins, when absent or defective, have been implicated in this disorder, and they together constitute the FA pathway, which functions in detection and repair of, and tolerance to, endogenous DNA damage. The damage primarily handled by the FA pathway has been assumed to be related to DNA interstrand crosslinks (ICLs). The FA pathway is activated upon ICL damage, and a hallmark of this activation is the mono-ubiquitination events of the key FANCD2-FANCI protein complex. Recent data have revealed unexpectedly complex details in the regulation of FA pathway activation by ICLs. In this short review, we summarize the knowledge accumulated over the years regarding how the FA pathway is activated via protein modifications.

    Original languageEnglish
    JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
    DOIs
    Publication statusAccepted/In press - 2017 Apr 14

    Fingerprint

    Fanconi Anemia
    Ubiquitination
    Phosphorylation
    Fanconi Anemia Complementation Group D2 Protein
    Bone Marrow Cells
    DNA Damage
    Carcinogenesis
    Proteins
    Stem Cells
    Genome
    DNA

    Keywords

    • DNA repair
    • Fanconi anemia
    • Interstrand crosslink
    • Mono-ubiquitination
    • Phosphorylation

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Health, Toxicology and Mutagenesis

    Cite this

    Activation of the FA pathway mediated by phosphorylation and ubiquitination. / Ishiai, Masamichi; Sato, Koichi; Tomida, Junya; Kitao, Hiroyuki; Kurumizaka, Hitoshi; Takata, Minoru.

    In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 14.04.2017.

    Research output: Contribution to journalArticle

    Ishiai, Masamichi ; Sato, Koichi ; Tomida, Junya ; Kitao, Hiroyuki ; Kurumizaka, Hitoshi ; Takata, Minoru. / Activation of the FA pathway mediated by phosphorylation and ubiquitination. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2017.
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    AU - Kurumizaka, Hitoshi

    AU - Takata, Minoru

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