Defining how problematic DNA replication impacts on chromosome segregation

题目：Defining how problematic DNA replication impacts on chromosome segregation

讲座人：Ian D. Hickson,  PhD FMedSci FRS, irector of the DNRF Center for Chromosome Stability, and Professor of Molecular Aging,Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark

时间：2018年10月26日，13:00-15:00

地点：生命科学学院邓祐才报告厅

联系人：徐冬一

Abstract:

Ultra-fine bridges (UFBs) are thin threads of DNA that connect the separating sister DNA masses in anaphase. They cannot be stained with DNA dyes and do not contain histones, making their detection problematic and dependent on immunofluorescence for associated proteins such as PICH or BLM. Nevertheless, they are very abundant, and are a feature of all anaphases. UFBs arise from specific loci that are characterized by the unusual sequence or structure: most notably, centromeres, the rDNA, telomeres and common fragile sites (CFSs). We are conducting a detailed analysis of two aspects of UFB biology: modeling the association of proteins to UFBs in vitro using optical tweezers, and investigating how unresolved UFBs affect cell division. In addition, through analysis of the underlying basis of UFB formation in human cells, we identified that CFSs and telomeres are still undergoing DNA synthesis in early mitosis in a process we term MiDAS. MiDAS depends upon a subset of homologous recombination factors, such as RAD52, but not RAD51/BRCA2, and appears to be a form of break-induced DNA replication. Inhibition of MiDAS leads to major chromosome segregation abnormalities. The latest progress on these projects will be presented.

题目：The impact of folate (叶酸) deficiency on the replication and segregation of the Fragile X trinucleotide repeat locus

主讲人：Ying Liu, MD PhDPrincipal Investigator in the DNRF Center for Chromosome Stability, and Associate, Professor in Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark

Abstract:

Tri-nucleotide repeat sequences (TNRs) can be problematic when they exceed a crucial threshold length. For example, if the TNR lies within a crucial gene, it can lead to gene silencing that then causes severe diseases, including neurodegeneration (reviewed in [1]). We will present our current research on how TNR regions are replicated in S phase and segregated in mitosis using Fragile X syndrome (FXS) cells as a model. FXS is caused by a CGG repeat in the FRAXA region on chromosome X. The repeat lies in the non-coding (5’ UTR) region of the Mental Retardation Gene 1 (FMR1). This TNR expands from the pre-mutation allele length (55-200 units) to a full mutation (200-4000 units) almost exclusively through maternal transmission [2, 3]. Interestingly, the fully mutated FRAXA region is prone to break when the cells are exposed to folic acid (叶酸) deficient growth medium, which is a phenomenon akin to that seen with common fragile sites (CFSs) in response to DNA replication stress. Our results indicate that folic acid deficiency could induce fragility and missegregation of the FRAXA locus in mitosis. Current studies are aimed at deciphering the mechanism underlying the instability of the long CGG repeats under folic acid deficiency conditions.

欢迎各位老师同学们积极参加!