Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins

Dantas, Tiago J.; Wang, Yifan; Lalor, Pierce; Dockery, Peter; Morrison, Ciarán

doi:10.1083/jcb.201012093

Cited by 51 publications

(54 citation statements)

References 73 publications

(107 reference statements)

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“…In contrast, hCetn-2 deletion in the human telomerase reverse transcriptase (hTERT)-immortalized retinal pigment epithelial cell line RPE1 affected not centrioles but instead cilogenesis (55). Moreover, centrosome duplication was not impaired by gene knockout of all three vertebrate centrins in chicken DT40 cells (56). Although altogether striking and puzzling, the latter finding is far from conclusive.…”

Section: Centrin and Centrin-binding Proteins At Human Centrosomesmentioning

confidence: 50%

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Rüthnick

Schiebel

2016

Molecular and Cellular Biology

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bThe yeast spindle pole body (SPB) is the functional equivalent of the mammalian centrosome. Centrosomes and SPBs duplicate exactly once per cell cycle by mechanisms that use the mother structure as a platform for the assembly of the daughter. The conserved Sfi1 and centrin proteins are essential components of the SPB duplication process. Sfi1 is an elongated molecule that has, in its center, 20 to 23 binding sites for the Ca 2؉ -binding protein centrin. In the yeast Saccharomyces cerevisiae, all Sfi1 N termini are in contact with the mother SPB whereas the free C termini are distal to it. During S phase and early mitosis, cyclin-dependent kinase 1 (Cdk1) phosphorylation of mainly serine residues in the Sfi1 C termini blocks the initiation of SPB duplication ("off" state). Upon anaphase onset, the phosphatase Cdc14 dephosphorylates Sfi1 ("on" state) to promote antiparallel and shifted incorporation of cytoplasmic Sfi1 molecules into the half-bridge layer, which thereby elongates into the bridge. The Sfi1 C termini of the two Sfi1 layers localize in the bridge center, whereas the N termini of the newly assembled Sfi1 molecules are distal to the mother SPB. These free Sfi1 N termini then assemble the new SPB in G 1 phase. Recruitment of Sfi1 molecules into the anaphase SPB and bridge formation were also observed in Schizosaccharomyces pombe, suggesting that the Sfi1 bridge cycle is conserved between the two organisms. Thus, restricting SPB duplication to one event per cell cycle requires only an oscillation between Cdk1 kinase and Cdc14 phosphatase activities. This clockwork regulates the "on"/"off" state of the Sfi1-centrin receiver.T he mammalian centrosome and the yeast spindle pole body (SPB) are both able to nucleate microtubules (MTs) from tubulin subunits and are therefore collectively named MT organizing centers (MTOCs). A second common feature is the duplication of the centrosome and SPB just once during each cell division cycle. In each case, it is the mother centrosome or SPB that provides the platform for the assembly of the daughter (1-3).In yeast, the SPB is absolutely critical for mitotic spindle formation and chromosome segregation. This is because alternative MT assembly pathways, such as the RCC1/Ran-GTP-or augmindependent MT nucleation pathways, are absent from yeast (4, 5). In contrast, human cells can assemble a mitotic spindle even in the absence of centrosomes because of centrosome-independent MT formation and the presence of spindle assembly pathways. Recent studies have shown that the ability of human cells to tolerate loss of centrosomes or centrosome overduplication is reliant upon the inactivation of the p53 tumor suppressor gene that otherwise arrests these abnormal cells in G 1 phase (6, 7). How cells sense centrosome number defects is currently not understood. Yet it is becoming clearer why such a surveillance mechanism is important. Centrosome overamplification may contribute to cell transformation or enhance the aggressive nature of already transformed cells (8, 9). It is therefore...

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Section: Centrin and Centrin-binding Proteins At Human Centrosomesmentioning

confidence: 50%

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Rüthnick

Schiebel

2016

Molecular and Cellular Biology

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“…4A). In a positive control experiment, CETN2-null RPE1 cells (Prosser and Morrison, 2015) showed an increased UV sensitivity, as had centrin-deficient chicken DT40 cells (Dantas et al, 2011). Furthermore, we observed no localisation of CEP164 to nuclear DNA damage foci marked by γ-H2AX after ionising radiation or UV treatment in RPE1 or HeLa cells with either of the two antibodies in immunofluorescence experiments (Fig.…”

Section: Resultsmentioning

confidence: 73%

CEP164-null cells generated by genome editing show a ciliation defect with intact DNA repair capacity

Daly

Gaboriau

Karakaya

et al. 2016

Journal of Cell Science

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Primary cilia are microtubule structures that extend from the distal end of the mature, mother centriole. CEP164 is a component of the distal appendages carried by the mother centriole that is required for primary cilium formation. Recent data have implicated CEP164 as a ciliopathy gene and suggest that CEP164 plays some roles in the DNA damage response (DDR). We used reverse genetics to test the role of CEP164 in the DDR. We found that conditional depletion of CEP164 in chicken DT40 cells using an auxin-inducible degron led to no increase in sensitivity to DNA damage induced by ionising or ultraviolet irradiation. Disruption of CEP164 in human retinal pigmented epithelial cells blocked primary cilium formation but did not affect cellular proliferation or cellular responses to ionising or ultraviolet irradiation. Furthermore, we observed no localisation of CEP164 to the nucleus using immunofluorescence microscopy and analysis of multiple tagged forms of CEP164. Our data suggest that CEP164 is not required in the DDR.

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“…Immunofluorescent cell staining was performed as described previously. 48 Cells were spotted onto poly-L-lysine-coated slides and fixed for 10 min in pre-chilled 95% methanol/5 mM EGTA at −20°C or 4% paraformaldehyde (PFA) at room temperature. Cells were permeabilized in 0.15% Triton X-100 in PBS for 2 min at room temperature if PFA fixation had been performed.…”

Section: Methodsmentioning

confidence: 99%

Promoter hijack reveals pericentrin functions in mitosis and the DNA damage response

et al. 2013

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Defective nucleotide excision repair with normal centrosome structures and functions in the absence of all vertebrate centrins

Abstract: Centrin-null cells undergo normal division but are highly sensitive to UV irradiation as a result of impaired DNA repair.

Cited by 51 publications

References 73 publications

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

Duplication of the Yeast Spindle Pole Body Once per Cell Cycle

CEP164-null cells generated by genome editing show a ciliation defect with intact DNA repair capacity

Promoter hijack reveals pericentrin functions in mitosis and the DNA damage response

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