Cleavage of BLM and Sensitivity of Bloom’s Syndrome Cells to Hydroxurea

Ababou, Mouna; Dumaire, Virginie; Amor‐Guéret, Mounira

doi:10.4161/cc.1.4.136

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…3D, right). Increasing amounts of cleaved forms of BLM (⌬BLM) and PARP (⌬PARP), characteristic of apoptosis (21), were detected between 4 and 48 hours after release (Fig. 3D, right).…”

Section: Resultsmentioning

confidence: 99%

A Major Role for Mitotic cdc2 Kinase Inactivation in the Establishment of the Mitotic DNA Damage Checkpoint

Bayart¹,

Grigorieva²,

Leibovitch

et al. 2004

Cancer Research

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Cdc2 kinase is inactivated when DNA damage occurs during the spindle assembly checkpoint. Here, we show that the level of mitotic Bloom syndrome protein phosphorylation reflects the level of cdc2 activity. A complete inactivation of cdc2 by either introduction of DNA doublestrand breaks or roscovitine treatment prevents exit from mitosis. Thus, mitotic cdc2 inactivation plays a major role in the establishment of the mitotic DNA damage checkpoint. In response to mitotic cdc2 inactivation, the M/G 1 transition is delayed after releasing the drug block in nonmalignant cells, whereas tumor cells exit mitosis without dividing and rereplicate their DNA, which results in mitotic catastrophe. This opens the way for new chemotherapeutic strategies.

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“…3D, right). Increasing amounts of cleaved forms of BLM (⌬BLM) and PARP (⌬PARP), characteristic of apoptosis (21), were detected between 4 and 48 hours after release (Fig. 3D, right).…”

Section: Resultsmentioning

confidence: 99%

A Major Role for Mitotic cdc2 Kinase Inactivation in the Establishment of the Mitotic DNA Damage Checkpoint

Bayart¹,

Grigorieva²,

Leibovitch

et al. 2004

Cancer Research

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“…Imamura et al reported that BLM-deficient cells generated from chicken DT40 B cells do not behave like BS cells since they do not express BLM mRNA but exhibit normal sensitivity to X-ray irradiation and HU and to be hypersensitive to UV exposure [4] . Ababou et al proposed that UV and HU appear to induce apoptosis through distinct pathways; induction of apoptosis in response to HU and ionizing radiation, but not UV, results from accumulation of DNA double-strand breaks [8] , which is clarified by further investigation.…”

Section: Discussionmentioning

confidence: 98%

Protein expression of BLM gene and its apoptosis sensitivity in hematopoietic tumor cell strains

Wang

2008

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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Patients with Bloom syndrome (BS) show an immunodeficiency, an enhanced sister chromatid exchanges (SCEs), a strong genetic instability and an increased predisposition to all. In order to investigate the differential expression of BLM protein in hematopoietic tumor cell strains and study the effects of BLM gene on ultraviolet (UV)-or hydroxyurea (HU)-induced apoptosis, Western blot was used to detect the expression of BLM protein in normal human bone marrow mononuclear cells and 4 kinds of hematopoietic tumor cell strains. The 4 kinds of hematopoietic tumor cells were exposed to UV light with a germicidal UV lamp or treated with 2 mmol/L hydroxyurea and the apoptotic rate was detected by using AnnexinV-FITC. The results showed that these tumor cells expressed BLM protein higher than the normal human bone marrow mononuclear cells (P<0.01). In the 4 hematopoietic tumor cells, BLM protein was all specially cleaved in response to UV-or HU-induced apoptosis. The increase of BLM protein expression may play an important role in the development of these tumors, and BLM proteolysis is likely to be a general feature of the apoptotic response.

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“…Samples equivalent to 2.5 10 5 cells were subjected to electrophoresis in NuPAGE Novex 4–12% Bis-Tris precast gels (Invitrogen). The procedures used for immunoblotting have been described elsewhere [23] .…”

Section: Methodsmentioning

confidence: 99%

Bloom’s Syndrome and PICH Helicases Cooperate with Topoisomerase IIα in Centromere Disjunction before Anaphase

et al. 2012

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Centromeres are specialized chromosome domains that control chromosome segregation during mitosis, but little is known about the mechanisms underlying the maintenance of their integrity. Centromeric ultrafine anaphase bridges are physiological DNA structures thought to contain unresolved DNA catenations between the centromeres separating during anaphase. BLM and PICH helicases colocalize at these ultrafine anaphase bridges and promote their resolution. As PICH is detectable at centromeres from prometaphase onwards, we hypothesized that BLM might also be located at centromeres and that the two proteins might cooperate to resolve DNA catenations before the onset of anaphase. Using immunofluorescence analyses, we demonstrated the recruitment of BLM to centromeres from G2 phase to mitosis. With a combination of fluorescence in situ hybridization, electron microscopy, RNA interference, chromosome spreads and chromatin immunoprecipitation, we showed that both BLM-deficient and PICH-deficient prometaphase cells displayed changes in centromere structure. These cells also had a higher frequency of centromeric non disjunction in the absence of cohesin, suggesting the persistence of catenations. Both proteins were required for the correct recruitment to the centromere of active topoisomerase IIα, an enzyme specialized in the catenation/decatenation process. These observations reveal the existence of a functional relationship between BLM, PICH and topoisomerase IIα in the centromere decatenation process. They indicate that the higher frequency of centromeric ultrafine anaphase bridges in BLM-deficient cells and in cells treated with topoisomerase IIα inhibitors is probably due not only to unresolved physiological ultrafine anaphase bridges, but also to newly formed ultrafine anaphase bridges. We suggest that BLM and PICH cooperate in rendering centromeric catenates accessible to topoisomerase IIα, thereby facilitating correct centromere disjunction and preventing the formation of supernumerary centromeric ultrafine anaphase bridges.

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Cleavage of BLM and Sensitivity of Bloom’s Syndrome Cells to Hydroxurea

Cited by 9 publications

References 14 publications

A Major Role for Mitotic cdc2 Kinase Inactivation in the Establishment of the Mitotic DNA Damage Checkpoint

A Major Role for Mitotic cdc2 Kinase Inactivation in the Establishment of the Mitotic DNA Damage Checkpoint

Protein expression of BLM gene and its apoptosis sensitivity in hematopoietic tumor cell strains

Bloom’s Syndrome and PICH Helicases Cooperate with Topoisomerase IIα in Centromere Disjunction before Anaphase

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