Function of MDC1/53BP1 sensor chaperone in radiation-induced chromatin repair

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The purpose of this study is to clarify the role of MDC1/53BP1 sensor chaperone on detection of chromatin damage and repair. In this study, a method by which phosphorylated histone H2AX foci and MDC1/53BP1 sensor chaperone foci can be detected was established.After X-irradiation, chromosome aberrations were induced. Immediately after irradiation, most of the chromosome aberration were chromatid-type, in contrast those detected 20 hours after irradiation were chromosome-type. the foci of phosphorylated histone H2AX were colocalized with chromatid-type aberrations immediately after irradiation, whereas the foci were colocalized with chromosome-type aberrations 20 hours after irradiation. These results indicate that the foci could persist or chromosomes without detectable breaks. It suggests that DNA damage checkpoint also senses chromatin damage, which is generated by mis-rejoining DNA double strand breaks.Furthermore, to know the function of MDC1/53BP1 sensor chaperone in the initial process of DNA/chromatin damage recognition, normal human cells harboring EGFP-53BP1 gene was established. Within 15 minutes after irradiation, EGFP-53BP1 foci were detected as tiny foci, but they grew thereafter, and 30 to 60 minutes after irradiation, they formed large foci, whose diameter was over 2 micrometer. Moreover, an inhibitor for ATM, KU55933, efficiently suppressed the foci of MDC1/53BP1 sensor chaperone. It clearly indicates that MDC1/53BP1 sensor chaperone foci formation is dependent on the ATM function.