DNA Double Strand Break Chromatin Alterations and Genome Integrity

尽管在正常和病理情况下对DNA损伤反应进行了广泛的研究， 对染色质重组如何响应DNA双链反应知之甚少 断裂（DSB）并有助于基因组维持和癌细胞适应性。现在有 强有力的证据表明DSB反应促进了更高级染色质结构的变化。 这部分是由DSB依赖的转录改变和DSB诱导的转录改变引起的。 不同染色体上同源基因组区域之间的重组。这项建议 利用几种新的方法来解决与争端解决机构之间的相互作用有关的问题， 染色质改变和基因组完整性。即，（i）DSB依赖的染色质如何 改变有助于转录基因沉默顺式DSB，以及（ii）如何DSB 诱导的染色体间端粒关联有助于基因组的完整性和生存？ 总的来说，这些研究将解决基因组完整性的基本问题， 辐射生物学与DSB反应和更高阶之间的通信有关 染色质结构

Despite extensive study of DNA damage responses in both normal and pathologic settings, it is poorly understood how chromatin reorganization occurs in response to DNA double-strand breaks (DSBs) and contributes to genome maintenance and cancer cell fitness. There is now strong evidence that DSB responses promote changes in higher order chromatin structure. These arise in part by DSB dependent alterations in transcription, and by DSB induced recombination between homologous genomic regions on different chromosomes. This proposal utilizes several novel approaches to address questions related to the interplay between DSB chromatin alterations and genome integrity. Namely, (i) How do DSB dependent chromatin alterations contribute to transcriptional gene silencing in cis to DSBs, and (ii) how do DSB induced inter-chromosomal telomere associations contribute to genome integrity and survival? Collectively, these investigations will address fundamental issues in genome integrity and radiation biology that are related to communication between DSB responses and higher order chromatin structure.