Checkpoint Arrest Signaling in Response to UV Damage Is Independent of Nucleotide Excision Repair in Saccharomyces cerevisiae

Zhang, Hong; Taylor, Jena; Siede, Wolfram

doi:10.1074/jbc.m300061200

Cited by 22 publications

(16 citation statements)

References 46 publications

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“…In addition, checkpoint activation in stationary phase (non-dividing) cultures suggests that unrepaired DNA damage triggers checkpoint activation rather than interference with replication or a DNA repair intermediate, although we cannot rule out a contribution from recombination repair. Similar observations have been made for UV-induced DNA damage (15). In humans, repair-proficient senescent cell cultures are characterized by phosphorylated Chk2 (the human Rad53p homolog), presumably due to telomere erosion (41).…”

Section: Discussionsupporting

confidence: 57%

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Spontaneous DNA Damage in Saccharomyces cerevisiae Elicits Phenotypic Properties Similar to Cancer Cells

Evert

Salmon

Song

et al. 2004

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 57%

“…Detection of Rad53 by Western Blotting-Yeast protein extracts were prepared following zirconium bead lysis in trichloroacetic acid and Rad53 was visualized by PAGE gel electrophoresis as described previously (15,16). The primary Rad53 antibody used was from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

Spontaneous DNA Damage in Saccharomyces cerevisiae Elicits Phenotypic Properties Similar to Cancer Cells

Evert

Salmon

Song

et al. 2004

Journal of Biological Chemistry

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“…It has been suggested that the DNA damage checkpoint monitors the presence of NER intermediates in UVirradiated G 1 and G 2 cells (5, 18-22, 49). However, other studies have suggested that the DNA damage checkpoint monitors pyrimidine dimers in the absence of NER (50,51). After a UV dose of 5 J͞m 2 , which is expected to introduce Ϸ400 pyrimidine dimers per cell, we found that the cell-cycle response of budding yeast and ⌬UVDE fission yeast, both of which excise UV lesions exclusively through NER, occurs only after passage through S phase.…”

Section: Discussionmentioning

confidence: 70%

UV irradiation induces a postreplication DNA damage checkpoint

Callegari

Kelly

2006

Proc. Natl. Acad. Sci. U.S.A.

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Eukaryotic cells irradiated with high doses of UV exhibit cell-cycle responses referred to as G 1͞S, intraS, and G2͞M checkpoints. After a moderate UV dose that approximates sunlight exposure and is lethal to fission yeast checkpoint mutants, we found unexpectedly that these cell-cycle responses do not occur. Instead, cells at all stages of the cell cycle carry lesions into S phase and delay cell-cycle progression for hours after the completion of bulk DNA synthesis. Both DNA replication and the checkpoint kinase, Chk1, are required to generate this cell-cycle response. UV-irradiation of ⌬chk1 cells causes chromosome damage and loss of viability only after cells have replicated irradiated DNA and entered mitosis. These data suggest that an important physiological role of the cell-cycle response to UV is to provide time for postreplication repair.cell cycle ͉ chk1 ͉ nucleotide excision repair ͉ yeast U V radiation from sunlight exposure induces DNA damage that is potentially lethal to cells and is carcinogenic to animals (1). Studies in fission and budding yeasts have demonstrated that genes that promote survival in UV light encode both DNA repair factors (2, 3) and checkpoint proteins that regulate the cell cycle in response to DNA damage (4, 5). These genes are conserved among eukaryotes, so diverse model systems may be used to address questions of molecular mechanism (6).The pyrimidine dimer is the most abundant form of DNA damage known to be induced by UV (7). This lesion is removed from duplex DNA by nucleotide excision repair (NER). When present during S phase, pyrimidine dimers cause gaps in the daughter DNA strand (8-12). The repair of these gaps is referred to as postreplication repair and involves bypass polymerases, homologous recombination, and other processes (13).Several eukaryotic cell-cycle responses have been observed after high-dose UV irradiation. Fission yeast UV-irradiated in G 2 delay the onset of mitosis, a response conserved in human cells that has been termed a G 2 ͞M DNA damage checkpoint (5, 14-16). It is posited that the UV sensitivity of fission yeast G 2 ͞M checkpoint mutants results from a failure to make time for the repair of UV-induced DNA lesions before mitosis (5). Budding yeast exhibit a G 1 ͞S checkpoint response that delays S phase entry after UV irradiation in G 1 (17). Because activation of the G 1 ͞S checkpoint requires NER genes, it has been suggested that the checkpoint monitors the presence of NER intermediates (12,(18)(19)(20). Mammalian cells exhibit a p53-dependent G 1 ͞S DNA damage checkpoint response that can eliminate damaged cells through apoptosis, delay entry into S phase, and facilitate NER (21). Like the G 1 ͞S checkpoint of yeast, the induction of p53 in G 1 requires NER and is independent of DNA replication (22). A NER-independent checkpoint is activated when UV lesions are present during S phase in Xenopus egg extracts and budding yeast NER mutants (18,23). In both model systems, UV lesions cause an arrest in S phase; however, this arrest appears to be ch...

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“…In yeast, however, the NER pathway does not actively recruit checkpoint signaling proteins that respond to UV damage. 7 …”

Section: Nucleotide Excision Repair and G 1 /S Checkpointmentioning

confidence: 99%

DNA Replication in the Face of (In)surmountable Odds

Cleaver

Laposa²,

Limoli³

2003

Cell Cycle

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"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material… Whether a specific enzyme is required to carry out the polymerization… remains to be seen." 1 ABSTRACTWe describe here a model for sequential recruitment of various enzymatic systems that maintain DNA replication fidelity in cells with damaged bases, especially those formed by ultraviolet (UV) irradiation. Systems of increasing complexity but decreasing fidelity are recruited to restore replication of damaged DNA. The first and most accurate response is nucleotide excision repair (NER) that is cell cycle-independent; next come various delaying cell cycle checkpoints that provide an extended time window for NER. These delay the onset of the S phase at the G 1 /S boundary, and inhibit the initiation of individual replicating units (replicons and clusters of replicons) within the S phase. When checkpoints fail to operate completely, DNA replication forks must negotiate damage and the loss of coding information on the parental DNA strands. Replication can be resumed using bypass polymerases, or alternative bypass mechanisms. Finally, if all else fails, replication forks may degrade to double strand breaks and recombinational processes then allow their reconstruction. A network of signaling kinases modulates the efficiency of many damage responsive proteins to tailor their activities and subcellular localizations by phosphorylation and dephosphorylation.

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Checkpoint Arrest Signaling in Response to UV Damage Is Independent of Nucleotide Excision Repair in Saccharomyces cerevisiae

Cited by 22 publications

References 46 publications

Spontaneous DNA Damage in Saccharomyces cerevisiae Elicits Phenotypic Properties Similar to Cancer Cells

Spontaneous DNA Damage in Saccharomyces cerevisiae Elicits Phenotypic Properties Similar to Cancer Cells

UV irradiation induces a postreplication DNA damage checkpoint

DNA Replication in the Face of (In)surmountable Odds

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