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- W2018720655 abstract "The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To date, no function has been assigned to nuclear TPX2. We now report that TPX2 plays a role in the cellular response to DNA double strand breaks induced by ionizing radiation. Loss of TPX2 leads to inordinately strong and transient accumulation of ionizing radiation-dependent Ser-139-phosphorylated Histone 2AX (γ-H2AX) at G(0) and G(1) phases of the cell cycle. This is accompanied by the formation of increased numbers of high intensity γ-H2AX ionizing radiation-induced foci. Conversely, cells overexpressing TPX2 have reduced levels of γ-H2AX after ionizing radiation. Consistent with a role for TPX2 in the DNA damage response, we found that the protein accumulates at DNA double strand breaks and associates with the mediator of DNA damage checkpoint 1 (MDC1) and the ataxia telangiectasia mutated (ATM) kinase, both key regulators of γ-H2AX amplification. Pharmacologic inhibition or depletion of ATM or MDC1, but not of DNA-dependent protein kinase (DNA-PK), antagonizes the γ-H2AX phenotype caused by TPX2 depletion. Importantly, the regulation of γ-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. In sum, our study identifies a novel and the first nuclear function for TPX2 in the cellular responses to DNA damage." @default.
- W2018720655 created "2016-06-24" @default.
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- W2018720655 date "2012-12-01" @default.
- W2018720655 modified "2023-10-12" @default.
- W2018720655 title "Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) Regulates γ-Histone 2AX (γ-H2AX) Levels upon Ionizing Radiation" @default.
- W2018720655 cites W1515564094 @default.
- W2018720655 cites W1537346008 @default.
- W2018720655 cites W1538419182 @default.
- W2018720655 cites W1544851750 @default.
- W2018720655 cites W1967803195 @default.
- W2018720655 cites W1974190379 @default.
- W2018720655 cites W1975248407 @default.
- W2018720655 cites W1978727038 @default.
- W2018720655 cites W1980017984 @default.
- W2018720655 cites W1985619216 @default.
- W2018720655 cites W1990387966 @default.
- W2018720655 cites W1991690400 @default.
- W2018720655 cites W1991948593 @default.
- W2018720655 cites W1992089991 @default.
- W2018720655 cites W1993188705 @default.
- W2018720655 cites W1996548153 @default.
- W2018720655 cites W1997294285 @default.
- W2018720655 cites W1998728980 @default.
- W2018720655 cites W1999084733 @default.
- W2018720655 cites W2000098053 @default.
- W2018720655 cites W2004351764 @default.
- W2018720655 cites W2015925058 @default.
- W2018720655 cites W2016529502 @default.
- W2018720655 cites W2022811243 @default.
- W2018720655 cites W2023179015 @default.
- W2018720655 cites W2023695022 @default.
- W2018720655 cites W2024781225 @default.
- W2018720655 cites W2029217345 @default.
- W2018720655 cites W2033475930 @default.
- W2018720655 cites W2033580919 @default.
- W2018720655 cites W2039143648 @default.
- W2018720655 cites W2039484278 @default.
- W2018720655 cites W2044873149 @default.
- W2018720655 cites W2045164156 @default.
- W2018720655 cites W2045563337 @default.
- W2018720655 cites W2046348382 @default.
- W2018720655 cites W2047599332 @default.
- W2018720655 cites W2048467789 @default.
- W2018720655 cites W2051003586 @default.
- W2018720655 cites W2051603299 @default.
- W2018720655 cites W2052036700 @default.
- W2018720655 cites W2060756795 @default.
- W2018720655 cites W2061920376 @default.
- W2018720655 cites W2065455422 @default.
- W2018720655 cites W2072155586 @default.
- W2018720655 cites W2075366096 @default.
- W2018720655 cites W2075981930 @default.
- W2018720655 cites W2077709632 @default.
- W2018720655 cites W2081164899 @default.
- W2018720655 cites W2087617976 @default.
- W2018720655 cites W2090108375 @default.
- W2018720655 cites W2093385884 @default.
- W2018720655 cites W2096509200 @default.
- W2018720655 cites W2097477376 @default.
- W2018720655 cites W2103926523 @default.
- W2018720655 cites W2108590463 @default.
- W2018720655 cites W2110817748 @default.
- W2018720655 cites W2120943086 @default.
- W2018720655 cites W2121075882 @default.
- W2018720655 cites W2121978205 @default.
- W2018720655 cites W2135794081 @default.
- W2018720655 cites W2137732261 @default.
- W2018720655 cites W2143629217 @default.
- W2018720655 cites W2145648841 @default.
- W2018720655 cites W2149249386 @default.
- W2018720655 cites W2154492966 @default.
- W2018720655 cites W2155819889 @default.
- W2018720655 cites W2157752802 @default.
- W2018720655 cites W2159803470 @default.
- W2018720655 cites W2159805523 @default.
- W2018720655 cites W2161489869 @default.
- W2018720655 cites W2162951729 @default.
- W2018720655 cites W2163367614 @default.
- W2018720655 cites W2165343647 @default.
- W2018720655 cites W2166065433 @default.
- W2018720655 cites W2167116134 @default.
- W2018720655 cites W2169911836 @default.
- W2018720655 cites W2170248514 @default.
- W2018720655 cites W2172147368 @default.
- W2018720655 cites W2266844879 @default.