 I'm Xiaonan. I'm working in Dr. Asting's lab. Our lab is interested on the causes and consequences of the Frederick X-related disorders. The Frederick X-related disorders comprise three distinct clinical conditions, including Frederick X syndrome, Frederick X associated tremor and tessier syndrome, and Frederick X associated primary ovarian insufficiency. All these three disorders are caused by expansion of a CGG repeat check in the five-pronged untranslated region in the FMR1 gene. The mechanism of repeat expansion is unknown. Our lab has developed a mouse model of Frederick X-related disorders to try to understand the mechanism of Frederick X repeat expansion. I'm working to try to understand the role of transcription couple repair in Frederick X repeat expansion. Transcription couple repair is a DNA repair pathway that only operates in actively transcribed gene. We first became interested in this pathway since previously we had finite expansion required transcription of FMR1 gene, or at least is present in transcriptionally competent chromatin. CSB is essential for transcription couple repair. In our previously paper, we had shown that CSB has gender and cell type specific effect of Frederick X repeat expansion. We had shown that loss of CSB reduces expansion frequency in somatic cells, but the situation in gene line is complicated. Loss of CSB had no effect on paternal transmission, but in maternal transmission, loss of CSB is associated with fewer expansion and more contractions in older models. How to interpret this data? One possibility is that CSB directly affect expansion, or CSB may protect the genome against contractions. They are also a third possibility, that is CSB protect the genome against expansion, but this effect is masked by the high frequency of expansion in males. In this current paper, we are trying to address these three possibilities. The complicated thing here is that we have both expansion and contraction. If we could find a system that has no expansion happened, it will be easier for us to see the effect on contraction, or a lower expansion frequency may allow us to see the effect on protecting the genome against expansion. Luckily, we have this system. It's the MSH2 mice. The null mice don't have any expansion. While in heterozygous animal, the expansion frequency is low, so we use the MSH2 CSB and our pre-mutational mice to answer our questions. Our current data, along with our previous data, suggests a model in which three different pathways compete for the instability substrate. The role of CSB in both contributing to and preventing expansion is not as paradoxical as it seems at first. We're thinking that CSB is acting outside of transcription couple repair to promote expansion via base excision repair, while CSB is acting to prevent expansion via its participation in a different pathway. Mechanism of repeat expansion has been studied for many years. Many unanswered questions remain. We hope that our finding will help us to understand the repeat expansion mechanism. Here, we invite you to read our paper. You may have your own interpretation of our data. If so, we welcome your input. We would like to discuss with our data further. Thank you very much and happy reading.