Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication

Kobayashi, Masahiko; Hirano, Atsushi; Kumano, Tomoyasu; Xiang, Shuang; Mihara, Kazuhiro; Haseda, Yasunari; Matsui, Osamu; Shimizu, Hiroko; Yamamoto, Ken

doi:10.1111/j.1356-9597.2004.00728.x

Cited by 41 publications

(42 citation statements)

References 41 publications

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“…Next, we generated a series of mutants in which individual phosphorylation sites were restored. Transient expression of wildtype Rad9 in Rad9 −/− DT40 cells (Kobayashi et al 2004) restored hydroxyurea (HU)-induced Chk1 phosphorylation to levels seen in parental (wild-type) DT40 cells (Fig. 1B), whereas Rad9-9A did not enhance Chk1 phosphorylation.…”

Section: Resultsmentioning

confidence: 99%

“…Rad9 is an integral part of the 9-1-1 clamp complex, which must be loaded onto chromatin by Rad17 to trigger Chk1 activation. To determine whether the Rad9-TopBP1 fusions also had to be loaded onto chromatin to enhance Chk1 phosphorylation, we expressed the Rad9-TopBP1 fusions in DT40 cells that lack Rad17 (Kobayashi et al 2004), the clamp loader for the 9-1-1 complex (Zou et al 2002Bermudez et al 2003;Ellison and Stillman 2003). As shown in Figure 3C, Rad17 −/− DT40 cells have a defect in HU-induced Chk1 phosphorylation that is corrected by expression of Rad17.…”

Section: Resultsmentioning

confidence: 99%

“…Wild-type, Rad9 −/− , and Rad17 −/− DT40 cells were grown as described previously (Kobayashi et al 2004). HEK293 cells (5 × 10 to 8 × 10 6 per transfection) were transfected by electroporation as described previously (Volkmer and Karnitz 1999) using a total of 40 µg of DNA per transfection and a 230-V, 20-msec pulse in a 0.4-cm cuvette with a BTX T 820 electroporator.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

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The Rad9–Hus1–Rad1 (9–1–1) clamp activates checkpoint signaling via TopBP1

Delacroix¹,

Wagner²,

Kobayashi³

et al. 2007

Genes Dev.

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422

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DNA replication stress triggers the activation of Checkpoint Kinase 1 (Chk1) in a pathway that requires the independent chromatin loading of the ATRIP-ATR (ATR-interacting protein/ATM [ataxia-telangiectasia mutated]-Rad3-related kinase) complex and the Rad9-Hus1-Rad1 (9-1-1) clamp. We show that Rad9's role in Chk1 activation is to bind TopBP1, which stimulates ATR-mediated Chk1 phosphorylation via TopBP1's activation domain (AD), a domain that binds and activates ATR. Notably, fusion of the AD to proliferating cell nuclear antigen (PCNA) or histone H2B bypasses the requirement for the 9-1-1 clamp, indicating that the 9-1-1 clamp's primary role in activating Chk1 is to localize the AD to a stalled replication fork.Supplemental material is available at http://www.genesdev.org.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cell Culture and Transfectionmentioning

confidence: 99%

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The Rad9–Hus1–Rad1 (9–1–1) clamp activates checkpoint signaling via TopBP1

Delacroix¹,

Wagner²,

Kobayashi³

et al. 2007

Genes Dev.

Self Cite

422

415

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“…Examination of genome stability in haploid yeast mutants defective for the 9-1-1 checkpoint complex has revealed modestly elevated levels of GCRs 1 (Myung et al 2001b). Mutation of vertebrate 9-1-1 complex subunits results in genome instability and lethality (Weiss et al 2000;Budzowska et al 2004;Hopkins et al 2004;Kobayashi et al 2004). Deficiency for mediators of the DNA damage response such as BRCA1 or BRCA2 also results in lethality accompanied by translocations, loss of chromosome arms, and aneuploidy (Venkitaraman 2002).…”

mentioning

confidence: 99%

Mutator Phenotype ofCaenorhabditis elegansDNA Damage Checkpoint Mutants

Harris¹,

Lowden²,

Clejan

et al. 2006

Genetics

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DNA damage response proteins identify sites of DNA damage and signal to downstream effectors that orchestrate either apoptosis or arrest of the cell cycle and DNA repair. The C. elegans DNA damage response mutants mrt-2, hus-1, and clk-2(mn159) displayed 8-to 15-fold increases in the frequency of spontaneous mutation in their germlines. Many of these mutations were small-to medium-sized deletions, some of which had unusual sequences at their breakpoints such as purine-rich tracts or direct or inverted repeats. Although DNA-damage-induced apoptosis is abrogated in the mrt-2, hus-1, and clk-2 mutant backgrounds, lack of the apoptotic branch of the DNA damage response pathway in cep-1/p53, ced-3, and ced-4 mutants did not result in a Mutator phenotype. Thus, DNA damage checkpoint proteins suppress the frequency of mutation by ensuring that spontaneous DNA damage is accurately repaired in C. elegans germ cells. Although DNA damage response defects that predispose humans to cancer are known to result in large-scale chromosome aberrations, our results suggest that small-to medium-sized deletions may also play roles in the development of cancer.

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“…Our genetic studies indicate that the C. elegans Rad17 homolog may function in the same pathway as the 9-1-1 complex with regard to repair of IR-induced DNA double-strand breaks ( Figure 1) and with regard to eliciting cell cycle arrest or apoptosis upon genotoxic stress (Figure 2). Thus, Rad17 may act via the 9-1-1 complex to initiate similar DNA damage signaling responses in vertebrates (Weiss et al 2003;Kobayashi et al 2004). …”

mentioning

confidence: 99%

The Caenorhabditis elegans Rad17 Homolog HPR-17 Is Required for Telomere Replication

Boerckel¹,

Walker

Ahmed

2007

Genetics

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Subunits of the Rad9/Rad1/Hus1 (9-1-1) proliferating cell nuclear antigen (PNCA)-like sliding clamp are required for DNA damage responses and telomerase-mediated telomere replication in the nematode Caenorhabditis elegans. PCNA sliding clamps are loaded onto DNA by a replication factor C (RFC) clamp loader. The C. elegans Rad17 RFC clamp loader homolog, hpr-17, functions in the same pathway as the 9-1-1 complex with regard to both the DNA damage response and telomerase-mediated telomere elongation. Thus, hpr-17 defines an RFC-like complex that facilitates telomerase activity in vivo in C. elegans.

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Critical role for chicken Rad17 and Rad9 in the cellular response to DNA damage and stalled DNA replication

Cited by 41 publications

References 41 publications

The Rad9–Hus1–Rad1 (9–1–1) clamp activates checkpoint signaling via TopBP1

The Rad9–Hus1–Rad1 (9–1–1) clamp activates checkpoint signaling via TopBP1

Mutator Phenotype ofCaenorhabditis elegansDNA Damage Checkpoint Mutants

The Caenorhabditis elegans Rad17 Homolog HPR-17 Is Required for Telomere Replication

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