The Schizosaccharomyces pombe rad3 checkpoint gene.

Bentley, Nicola J.; Holtzman, Douglas A.; Flaggs, G.; Keegan, Kathleen; Demaggio, Anthony J.; Ford, Jon C.; Hoekstra, Merl F.; Carr, Antony

doi:10.1002/j.1460-2075.1996.tb01054.x

Cited by 342 publications

(326 citation statements)

References 54 publications

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“…One result consistent with the model of sustained upstream signaling is that inactivation of the fission yeast mediator protein Cut5 (homolog of TopBP1) results in premature checkpoint termination [21]. However, similar experiments with the ATR homolog Rad3 show a sustained checkpoint response [22], so additional experiments are warranted to clarify this model.…”

Section: Dephosphorylation Of Other Checkpoint Proteinsmentioning

confidence: 83%

Turning off the G2 DNA damage checkpoint

Calonge

O’Connell

2008

DNA Repair

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In response to DNA damage, cells activate checkpoints to delay cell cycle progression and allow time for completion of DNA repair before commitment to S-phase or mitosis. During G2, many proteins collaborate to activate Chk1, an effector protein kinase that ensures the mitotic cyclindependent kinase remains in an inactive state. This checkpoint is ancient in origin and highly conserved from fission yeast to humans. Work from many groups has led to a detailed description of the spatiotemporal control of signaling events leading to Chk1 activation. However, to survive DNA damage in G2, the checkpoint must be inactivated to allow resumption of cell cycling and entry into mitosis. Though only beginning to be understood, here we review current data regarding checkpoint termination signals acting on Chk1 and its' upstream regulators.

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Section: Dephosphorylation Of Other Checkpoint Proteinsmentioning

confidence: 83%

Turning off the G2 DNA damage checkpoint

Calonge

O’Connell

2008

DNA Repair

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“…Irradiation of cells leads to phosphorylation of chk1 itself, and this response requires all of the upstream checkpoint components, including rad3 (Walworth and Bernards, 1996). The rad3 gene is related in sequence and function to several cell cycle control genes including ESRI (MECI) (S. cerevisiae), mei-41 (Drosophila) and the human genes ATR and ATM (Zakian, 1995;Lavin et al, 1995;Bentley et al, 1996). Accordingly, it seemed likely that hchk1 might operate downstream from ATM in G2 checkpoint control.…”

Section: Discussionmentioning

confidence: 99%

Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia-telangiectasia cells

et al. 1999

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Cells from patients with the human genetic disorder ataxia-telangiectasia (A-T) are defective in the activation of cell cycle checkpoints in response to ionizing radiation damage. In order to understand the role of ATM in checkpoint control we investigated whether Schizosaccaromyces pombe chk1, a protein kinase implicated in controlling the G2 DNA damage checkpoint, might alter the radiosensitive phenotype in A-T cells. The ®ssion yeast chk1 gene was cloned into an EBV-based vector under the control of a metallothionein promoter and transfected into A-T lymphoblastoid cells. Induction of chk1 enhanced the survival of an A-T cell line in response to radiation exposure as determined by cell viability and reduction of radiation-induced chromosome aberrations. This can be accounted for at least in part by the restoration of the G2 checkpoint to chk1 expressing cells. There was no evidence that chk1 expression corrected either the G1/S checkpoint or radioresistant DNA synthesis in S phase in these cells. These results suggest that chk1 when overexpressed acts downstream from ATM to restore the G2 checkpoint in these cells and correct the radiosensitive phenotype. These data allow us to dissociate individual checkpoint events and relate them to the radiosensitive phenotype in A-T cells.

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“…Vpr still induced G2 arrest in cells from patients with ataxia telangiectasia (AT) [40]. These AT cells are mutant for the ATM gene, which is a human homologue of fission yeast Rad3, and they do not arrest in G2 in response to DNA damage caused by ionizing radiation [47][48][49]. However, recent reports show that Vpr activates ATR, the second human homologue of fission yeast Rad3, and other steps in this checkpoint pathway such as RAD17, HUS1, BRCA1 and γ-H2AX [50,51].…”

Section: Cell Cycle G2/m Arrest Induced By Hiv-1 Vprmentioning

confidence: 99%

Viral infections and cell cycle G2/M regulation

Zhao

Elder

2005

Cell Res

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Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. In both human and fission yeast (Schizosaccharomyces pombe) cells, the activity of Cdc2 is regulated in part by the phosphorylation status of tyrosine 15 (Tyr15) on Cdc2, which is phosphorylated by Wee1 kinase during late G2 and is rapidly dephosphorylated by the Cdc25 tyrosine phosphatase to trigger entry into mitosis. These Cdc2 regulators are the downstream targets of two wellcharacterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. Increasing evidence suggests that Cdc2 is also commonly targeted by viral proteins, which modulate host cell cycle machinery to benefit viral survival or replication. In this review, we describe the effect of viral protein R (Vpr) encoded by human immunodeficiency virus type 1 (HIV-1) on cell cycle G2/M regulation. Based on our current knowledge about this viral effect, we hypothesize that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. One the unique features distinguishing Vpr-induced G2 arrest from the classic checkpoints is the role of phosphatase 2A (PP2A) in Vpr-induced G2 arrest. Interestingly, PP2A is targeted by a number of other viral proteins including SV40 small T antigen, polyomavirus T antigen, HTLV Tax and adenovirus E4orf4. Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions.

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The Schizosaccharomyces pombe rad3 checkpoint gene.

Cited by 342 publications

References 54 publications

Turning off the G2 DNA damage checkpoint

Turning off the G2 DNA damage checkpoint

Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia-telangiectasia cells

Viral infections and cell cycle G2/M regulation

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