human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: DNA double-strand breaks ( DSBs ) trigger ATM ( ataxia telangiectasia mutated ) signalling and elicit genomic rearrangements and chromosomal fragmentation if misrepaired or unrepaired . Although most DSB repair is ATM-independent , approximately 15% of ionizing radiation ( IR)-induced breaks persist in the absence of ATM-signalling. 53BP1 ( p53-binding protein 1 ) facilitates ATM-dependent DSB repair but is largely dispensable for ATM activation or checkpoint arrest . ATM promotes DSB repair within heterochromatin by phosphorylating KAP-1 ( KRAB-associated protein 1 , also known as TIF1beta , TRIM28 or KRIP-1 ; ref. 2 ) . Here , we show that the ATM signalling mediator proteins MDC1 , RNF8 , RNF168 and 53BP1 are also required for heterochromatic DSB repair . Although KAP-1 phosphorylation is critical for 53BP1-mediated repair , overall phosphorylated KAP-1 ( pKAP-1 ) levels are only modestly affected by 53BP1 loss. pKAP-1 is transiently pan-nuclear but also forms foci overlapping with gammaH2AX in heterochromatin . Cells that do not form 53BP1 foci , including human RIDDLE ( radiosensitivity , immunodeficiency , dysmorphic features and learning difficulties ) syndrome cells , fail to form pKAP-1 foci. 53BP1 amplifies Mre11-NBS1 accumulation at late-repairing DSBs , concentrating active ATM and leading to robust , localized pKAP-1 . We propose that ionizing-radiation induced foci ( IRIF ) spatially concentrate ATM activity to promote localized alterations in regions of chromatin otherwise inhibitory to repair .
    OUTPUT:

agent
genomic instability and mutation
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: DNA double-strand breaks ( DSBs ) trigger ATM ( ataxia telangiectasia mutated ) signalling and elicit genomic rearrangements and chromosomal fragmentation if misrepaired or unrepaired . Although most DSB repair is ATM-independent , approximately 15% of ionizing radiation ( IR)-induced breaks persist in the absence of ATM-signalling. 53BP1 ( p53-binding protein 1 ) facilitates ATM-dependent DSB repair but is largely dispensable for ATM activation or checkpoint arrest . ATM promotes DSB repair within heterochromatin by phosphorylating KAP-1 ( KRAB-associated protein 1 , also known as TIF1beta , TRIM28 or KRIP-1 ; ref. 2 ) . Here , we show that the ATM signalling mediator proteins MDC1 , RNF8 , RNF168 and 53BP1 are also required for heterochromatic DSB repair . Although KAP-1 phosphorylation is critical for 53BP1-mediated repair , overall phosphorylated KAP-1 ( pKAP-1 ) levels are only modestly affected by 53BP1 loss. pKAP-1 is transiently pan-nuclear but also forms foci overlapping with gammaH2AX in heterochromatin . Cells that do not form 53BP1 foci , including human RIDDLE ( radiosensitivity , immunodeficiency , dysmorphic features and learning difficulties ) syndrome cells , fail to form pKAP-1 foci. 53BP1 amplifies Mre11-NBS1 accumulation at late-repairing DSBs , concentrating active ATM and leading to robust , localized pKAP-1 . We propose that ionizing-radiation induced foci ( IRIF ) spatially concentrate ATM activity to promote localized alterations in regions of chromatin otherwise inhibitory to repair .
    OUTPUT:
