Critical Role for Mouse Hus1 in an S-Phase DNA Damage Cell Cycle Checkpoint

Weiss, Robert S.; Leder, Philip; Vaziri, Cyrus

doi:10.1128/mcb.23.3.791-803.2003

Cited by 70 publications

(83 citation statements)

References 67 publications

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“…65 The absence of Hus1 in embryonic fibroblasts causes a block of proliferation due to chromosomal abnormalities similar to those seen in ATR depleted cells. However, Hus1 -/-p21 -/-double null fibroblasts show restored proliferation 66,67 suggesting a link between chromatin binding proteins and p21 signaling pathway. Our results show that p38 kinase is important component in the activation of a p21-dependent pathway in the absence of ATR kinase activity in embryonic stem cells.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the ATR/Chk1 Pathway Induces a p38-Dependent S-phase Delay in Mouse ES Cells

Jirmanova

Bulavin²,

Fornace³

2005

Cell Cycle

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Section: Discussionmentioning

confidence: 99%

Inhibition of the ATR/Chk1 Pathway Induces a p38-Dependent S-phase Delay in Mouse ES Cells

Jirmanova

Bulavin²,

Fornace³

2005

Cell Cycle

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“…HUS1 lies within the amplified region at 7p13; considerable evidence ties HUS1 with genomic instability This gene is essential for a functional DNA damage checkpoint response, and cells lacking HUS1 are hypersensitive to ionizing radiation and UV [30,31]. Weiss et al have reported how inactivation of HUS1 in mice results in increased chromosomal abnormalities [32] Hus1 forms a checkpoint complex with rad9 and rad1 that is involved in DNA repair itself [33].…”

Section: Chromosomementioning

confidence: 99%

aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: Coordinate involvement of the regions including BCR and ABL

Bartos

Gaile

McQuaid

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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In order to identify small regions of the genome whose specific copy number alteration is associated with high genomic instability in the form of overall genome-wide copy number aberrations, we have analyzed array-based comparative genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy number changes of a small number of specific regions were significantly correlated with elevated overall amplifications and deletions scattered throughout the entire genome. One significant region at 9q34 includes the c-ABL gene Another region spanning 22q11-13 includes the breakpoint cluster region (BCR) of the Philadelphia chromosome Coordinate 22q11-13 alterations were observed in nine of eleven tumors with the 9q34 alteration Additional regions on 1q and 14q were associated with overall genome-wide copy number changes, while copy number aberrations on chromosome 7p, 7q, and 13q21.1-31.3 were found associated with this instability only in tumors from patients with a smoking history Our analysis demonstrates there are a small number of regions of the genome where gain or loss is commonly associated with a tumor's overall level of copy number aberrations Our finding BCR and ABL located within two of the instability-associated regions, and the involvement of these two regions occurring coordinately, suggests a system akin to the BCR-ABL translocation of CML may be involved in genomic instability in about one-third of human colorectal carcinomas.

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“…However, cells deficient in the ATR-pathway proteins Hus1 (28) and Chk1 (15) have been studied, and ATR has thus been implicated, albeit indirectly, in the inhibition of origin firing after UV and aphidicolin treatment. Future work will use the fiber labeling technique described here, together with recent advances in recombinational knockout and/or small interfering RNA technology, to make a direct comparison of each replication phenomenon separately in checkpoint-competent versus specifically checkpoint-compromised mammalian cells.…”

Section: Effects Of Ir Mms and Hu On Replication Dynamics: Mammaliamentioning

confidence: 99%

Visualization of Altered Replication Dynamics after DNA Damage in Human Cells

Merrick

Jackson

Diffley

2004

Journal of Biological Chemistry

213

186

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Eukaryotic cells respond to DNA damage within the S phase by activating an intra-S checkpoint: a response that includes reducing the rate of DNA synthesis. In yeast cells this can occur via checkpoint-dependent inhibition of origin firing and stabilization of ongoing forks, together with a checkpoint-independent slowing of fork movement. In higher eukaryotes, however, the mechanism by which DNA synthesis is reduced is less clear. We have developed strategies based on DNA fiber labeling that allow the quantitative assessment of rates of replication fork movement, origin firing, and fork stalling throughout the genome by examining large numbers of individually labeled replication forks. We show that exposing S phase cells to ionizing radiation induces a transient block to origin firing but does not affect fork rate or fork stalling. Alkylation damage by methyl methane sulfonate causes a slowing of fork movement and a high rate of fork stalling, in addition to inducing a block to new origin firing. Nucleotide depletion by hydroxyurea also reduces replication fork rate and increases stalling; moreover, in contrast to a recent report, we show that hydroxyurea induces a strong block to new origin firing. The DNA fiber labeling strategy provides a powerful new approach to analyze the dynamics of DNA replication in a perturbed S phase.

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Critical Role for Mouse Hus1 in an S-Phase DNA Damage Cell Cycle Checkpoint

Cited by 70 publications

References 67 publications

Inhibition of the ATR/Chk1 Pathway Induces a p38-Dependent S-phase Delay in Mouse ES Cells

Inhibition of the ATR/Chk1 Pathway Induces a p38-Dependent S-phase Delay in Mouse ES Cells

aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: Coordinate involvement of the regions including BCR and ABL

Visualization of Altered Replication Dynamics after DNA Damage in Human Cells

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