Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks

Leskovac, Andreja; Vujić, Dragana; Guć-Šćekić, Marija; Petrović, Suzana; Joksić, Ivana; Slijepčević, Predrag; Joksić, Gordana

doi:10.1620/tjem.221.69

Cited by 15 publications

(7 citation statements)

References 22 publications

(29 reference statements)

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“…First, there is a delay in the disappearance of γ-H2AX foci induced by cisplatin or IR in cells treated with FAN1 siRNA compared with control cells. Similar results were reported recently in FA cells (Leskovac et al, 2010). At all time points during recovery from cisplatin and IR, there are more RAD51 foci in FAN1-depleted cells than in control cells (Figure 7C).…”

Section: Discussionsupporting

confidence: 93%

Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2

Mackay

Déclais

Lundin

et al. 2010

Cell

282

356

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DNA interstrand crosslinks (ICLs) are highly toxic because they block the progression of replisomes. The Fanconi Anemia (FA) proteins, encoded by genes that are mutated in FA, are important for repair of ICLs. The FA core complex catalyzes the monoubiquitination of FANCD2, and this event is essential for several steps of ICL repair. However, how monoubiquitination of FANCD2 promotes ICL repair at the molecular level is unknown. Here, we describe a highly conserved protein, KIAA1018/MTMR15/FAN1, that interacts with, and is recruited to sites of DNA damage by, the monoubiquitinated form of FANCD2. FAN1 exhibits endonuclease activity toward 5' flaps and has 5' exonuclease activity, and these activities are mediated by an ancient VRR_nuc domain. Depletion of FAN1 from human cells causes hypersensitivity to ICLs, defects in ICL repair, and genome instability. These data at least partly explain how ubiquitination of FANCD2 promotes DNA repair.

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Section: Discussionsupporting

confidence: 93%

Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2

Mackay

Déclais

Lundin

et al. 2010

Cell

282

356

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“…The repair kinetics of radiation-induced DSBs were assessed in primary fibroblasts from Fanconi anemia, non-fanconic anemia bone marrow failure (non-FABMF) and control cell lines based on a gH2AX assay. Twenty-four hours after exposure to 2 Gy of IR, the level of gH2AX foci per cell in Fanconi anemia cell lines was approximately 2.5-fold higher compared to that in non-FABMF patients, and approximately 8-fold higher when compared with non-irradiated controls [103]. Fanconi anemia fibroblasts retained an elevated level of residual gH2AX foci after 24 h IR exposure, suggesting that the persistence of gH2AX foci could be a reliable measure to diagnose Fanconi anemia from non-FABMF and controls.…”

Section: Fibroblastsmentioning

confidence: 88%

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Siddiqui

François

Fenech

et al. 2015

Mutation Research/Reviews in Mutation Research

167

142

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“…The assay has already successfully identified AT, NBS, xeroderma pigmentosum, FA, retinoblastoma, Ligase IV syndrome patients and others [114; 119; 120; 121; 122]. Recently, the new translational opportunities of the γ-H2AX assay attracted attention of several international groups, but the reported results are somewhat contradictory.…”

Section: Individual Radiosensitivitymentioning

confidence: 99%

Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research

et al. 2012

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Formation of γ-H2AX in response to DNA double stranded breaks (DSBs) provides the basis for a sensitive assay of DNA damage in human biopsies. The review focuses on the application of γ-H2AX-based methods to translational studies to monitor the clinical response to DNA targeted therapies such as some forms of chemotherapy, external beam radiotherapy, radionuclide therapy or combinations thereof. The escalating attention on radiation biodosimetry has also highlighted the potential of the assay including renewed efforts to assess the radiosensitivity of prospective radiotherapy patients. Finally the γ-H2AX response has been suggested as a basis for an in vivo imaging modality.

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Fanconi Anemia Is Characterized by Delayed Repair Kinetics of DNA Double-Strand Breaks

Cited by 15 publications

References 22 publications

Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2

Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research

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