Histone H2A variants H2AX and H2AZ

Redon, Christophe E.; Pilch, Duane R.; Rogakou, Emmy P.; Sedelnikova, Olga A.; Newrock, Kenneth M.; Bonner, William M.

doi:10.1016/s0959-437x(02)00282-4

Cited by 693 publications

(539 citation statements)

References 45 publications

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“…At 5 kJ/m 2 , the absolute number of crosslinks is lower and the relative ratio of monoadducts to crosslinks is higher than at 20 kJ/m 2 UVA [9,41]. γ-H2AX was barely detectable at 1.5 and 3 h following HMT and UVA treatment, but increased monotonically over 9 h. These results contrast with the almost immediate appearance of γ-H2AX following ionizing radiation [35,42] (Fig. 1) and are consistent with the generation of DSB not as an immediate DNA lesion of HMT photoadducts but rather as an intermediate in response to ICL.…”

Section: Uva Dose-and Time-dependence Of γ-H2ax Formation Due To Iclmentioning

confidence: 76%

“…The formation of phosphorylated histone H2AX (γ-H2AX) has been widely used as a marker for the presence of DSB in general [35,36], as well as specifically following processing of ICL [32,33]. In the present study, we systematically monitored the formation of γ-H2AX following ICL generated by psoralen or mitomycin C in normal and NERdeficient human fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

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γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

Mogi

2006

DNA Repair

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To further define the molecular mechanisms involved in processing interstrand crosslinks, we monitored the formation of phosphorylated histone H2AX (γ-H2AX), which is generated in chromatin near double strand break sites, following DNA damage in normal and repair-deficient human cells. Following treatment with a psoralen derivative and ultraviolet A radiation doses that produce significant numbers of crosslinks, γ-H2AX levels in nucleotide excision repair-deficient XP-A fibroblasts (XP12RO-SV) increased to levels that were twice those observed in normal control GM637 fibroblasts. A partial XPA revertant cell line (XP129) that is proficient in crosslink removal, exhibited reduced γ-H2AX levels that were intermediate between those of GM637 and XP-A cells. XP-F fibroblasts (XP2YO-SV and XP3YO) that are also repair-deficient exhibited γ-H2AX levels below even control fibroblasts following treatment with psoralen and ultraviolet A radiation. Similarly, another crosslinking agent, mitomycin C, did not induce γ-H2AX in XP-F cells, although it did induce equivalent levels of γ-H2AX in XPA and control GM637 cells. Ectopic expression of XPF in XP-F fibroblasts restored γ-H2AX induction following treatment with crosslinking agents. Angelicin, a furocoumarin which forms only monoadducts and not crosslinks following ultraviolet A radiation, as well as ultraviolet C radiation, resulted only in weak induction of γ-H2AX in all cells, suggesting that the double strand breaks observed with psoralen and ultraviolet A treatment result preferentially following crosslink formation. These results indicate that XPF is required to form γ-H2AX and likely double strand breaks in response to interstrand crosslinks in human cells. Furthermore, XPA may be important to allow psoralen interstrand crosslinks to be processed without forming a double strand break intermediate.

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Section: Uva Dose-and Time-dependence Of γ-H2ax Formation Due To Iclmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

Mogi

2006

DNA Repair

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“…To examine whether the defective cell-cycle arrest in BubR1 þ /À cells was accompanied by a weakened DNA damage response, we analysed the level of phosphohistone 2AX (p-H2AX), a marker tightly associated with the extent of DNA damage (Redon et al, 2002), in paired MEFs treated with doxorubicin for various intervals. Whereas little p-H2AX was detectable in untreated wild-type or BubR1 þ /À MEFs, much stronger H2AX phosphorylation was induced by doxorubicin treatment (Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

BubR1 is involved in regulation of DNA damage responses

Fang

Wang

et al. 2006

Oncogene

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“…After irradiation, histone H2AX is phosphorylated and assembles into nuclear foci at the DSB sites (Redon et al, 2002;Aten et al, 2004). Unirradiated cells in S phase exhibited fluorescence.…”

Section: Resultsmentioning

confidence: 99%

XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells

et al. 2006

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Non-homologous end joining (NHEJ) and homologous recombination (HR) are two pathways that can compete or cooperate for DNA double-strand break (DSB) repair. NHEJ was previously shown to act throughout the cell cycle whereas HR is restricted to late S/G2. Paradoxically, we show here that defect in XRCC4 (NHEJ) leads to over-stimulation of HR when cells were irradiated in G1, not in G2. However, XRCC4 defect did not modify the strict cell cycle regulation for HR (i.e. in S/G2) as attested by (i) the formation of Rad51 foci in late S/G2 whatever the XRCC4 status, and (ii) the fact that neither Rad51 foci nor HR (gene conversion plus single-strand annealing) events induced by ionizing radiation were detected when cells were maintained blocked in G1. Finally, both c-H2AX analysis and pulse field gel electrophoresis showed that following irradiation in G1, some DSBs reached S/G2 in NHEJ-defective cells. Taken together, our results show that when cells are defective in G1/S arrest, DSB produced in G1 and left unrepaired by XRCC4 can be processed by HR but in late S/G2.

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Histone H2A variants H2AX and H2AZ

Cited by 693 publications

References 45 publications

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

γ-H2AX formation in response to interstrand crosslinks requires XPF in human cells

BubR1 is involved in regulation of DNA damage responses

XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells

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