Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

Liu, Jen-Sing; Kuo, Shu-Ru; Melendy, Thomas

doi:10.1016/j.mrfmmm.2003.08.018

Cited by 45 publications

(45 citation statements)

References 61 publications

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“…A DNA damage response can also be visualized by accumulation of the variant histone protein, H2AX, which is phosphorylated at the γ position (γH2AX) at sites of DNA damage and repair. 50,51 Consistent with the HU results, approximately 54.8 ± 3.1% of Id3-infected β-cells also expressed nuclear γH2AX, compared with fewer than 2.6 ± 1.3% of LacZ-infected β-cells (Fig. 3A-C).…”

Section: E and F)supporting

confidence: 86%

“…Similarly, histone H2AX is rapidly phosphorylated 52 in response to S phase DNA doublestrand breaks. 51,72 Thus, our observation that γH2AX colocalized with foci containing BrdU and that 53BP1 relocalized in Id3-expressing β-cells is entirely consistent with a repair response. Further evidence for a repair response in Id3 expressing β-cells came from hydroxyurea treatment (HU) which preferentially inhibits BrdU incorporation in replicating cells.…”

Section: Disclosure Of Potential Conflicts Of Interestsupporting

confidence: 66%

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Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

Lee

Hao

Levine

et al. 2011

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Section: E and F)supporting

confidence: 86%

Section: Disclosure Of Potential Conflicts Of Interestsupporting

confidence: 66%

Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

Lee

Hao

Levine

et al. 2011

Islets

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“…2, panels A and B; Supplemental Figure 3A). UVA induction of γ-H2AX foci formation was previously shown [44] and is probably the consequence of oxidized DNA lesions [45,46] creating sites of single strand DNA and/or stalled replication forks that could also be sites for γ-H2AX foci formation [47][48][49][50]. UVA treated wild-type and Aag−/− cell cultures had many cells with 11-30 foci per cell by 6 hours after treatment (data not shown) but very few cells with >50 foci per cell (12% for both wild-type and Aag−/−; Fig.…”

Section: Induction Of γ-H2ax Foci Following Uva Irradiationmentioning

confidence: 88%

“…However, γ-H2AX foci have also been shown to be induced by agents that do not cause DSBs directly, such as UVA [44], MMS [47][48][49]54,55], and Angelicin [19]. In these cases it is believed that either the formation of a single strand break generated during the processing of oxidized or alkylated DNA bases subsequently lead to DSBs [55], or that γ-H2AX foci can be formed at sites of ssDNA, and/or at stalled replication forks [47][48][49][50]. In our experiments we see a maximal induction of γ-H2AX foci 28 hours after TMP+UVA treatment that would be expected for DSB formation as a part of the ICL repair mechanism [14].…”

Section: Discussionmentioning

confidence: 99%

“…3C and 4) Angelicin+UVA treatment led to significant foci induction. As for some other DNA damaging agents, the formation of monoadducts can block replication forks and γ-H2AX foci will be formed at these sites [47][48][49]. Another possibility is that closely opposed single strand breaks that arise from processing of closely opposed monoadducts may go on to form a DSB.…”

Section: γ-H2ax Foci Formation and Disappearance Is Similar In Wild-tmentioning

confidence: 99%

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3-Methyladenine DNA glycosylase is important for cellular resistance to psoralen interstrand cross-links

et al. 2008

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DNA interstrand cross-links (ICLs), widely used in chemotherapy, are cytotoxic lesions because they block replication and transcription. Repair of ICLs involves proteins from different repair pathways however the precise mechanism is still not completely understood. Here, we report that the 3-methyladenine DNA glycosylase (Aag), an enzyme that initiates base excision repair at a variety of alkylated bases, is also involved plays a role in the repair of ICLs. Aag−/− mouse embryonic stem cells were shown to be more sensitive to the cross-linking agent 4, 5', 8-trimethylpsoralen than wildtype cells, but no more sensitive than wild-type to the psoralen derivative Angelicin that forms only monoadducts. We show that γ-H2AX foci formation, a marker for double strand breaks that are formed during ICL repair, is impaired in psoralen treated Aag−/− cells in both quantity and kinetics. However, in our in vitro system, purified human AAG can neither bind to the ICL nor cleave it. Taken together, our results suggest that Aag is important for the resistance of mouse ES cells to psoralen-induced ICLs. has a role in the repair of ICLs in mouse ES cells, but that its involvement may be indirect, perhaps mediated through interaction with other proteins, or by its action on an intermediate of ICL repair.

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Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis

et al. 2006

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Background: DNA replication stress often induces DNA damage. The antitumor drug hydroxyurea (HU), a potent inhibitor of ribonucleotide reductase that halts DNA replication through its effects on cellular deoxynucleotide pools, was shown to damage DNA inducing double-strand breaks (DSBs). Aphidicolin (APH), an inhibitor of a-like DNA polymerases, was also reported to cause DNA damage, but the evidence for induction of DSBs by APH is not straightforward. Histone H2AX is phosphorylated on Ser 139 in response to DSBs and one of the protein kinases that phosphorylate H2AX is ataxia telangiectasia mutated (ATM); activation of ATM is through its phosphorylation of Ser 1981. The present study was undertaken to reveal whether H2AX is phosphorylated in cells exposed to HU or APH and whether its phosphorylation is mediated by ATM. Materials and Methods: HL-60 cells were treated in cultures with 0.1-5.0 mM HU or 1-4 lM APH for up to 5 h. Activation of ATM and H2AX phosphorylation was detected immunocytochemically using Ab specific to Ser1981-ATM or Ser 139-H2AX epitopes, respectively, concurrent with measurement of cellular DNA content. Results: While exposure of cells to HU led to H2AX phosphorylation selectively during S phase and the cells progressing through the early portion of S (DI 5 1.1-1.4) were

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Comparison of checkpoint responses triggered by DNA polymerase inhibition versus DNA damaging agents

Cited by 45 publications

References 61 publications

Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

3-Methyladenine DNA glycosylase is important for cellular resistance to psoralen interstrand cross-links

Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis

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