Ying Liu – University of Copenhagen

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Ying Liu

Repetitive sequences constitute 30% of the genome and are the common source of diversity. The tri-nucleotide repeat (TNR) is one type of repeat and can be problematic when it exceeds a crucial threshold length. For example, if the TNR lies within a crucial gene, it can cause severe disease (reviewed in [1]). The mechanisms underlying the diseases associated with TNRs are not fully understood, and DNA replication and repair pathways are speculated to play an important role in their development. One of our current research focuses is to study how the TNR regions are replicated 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 deficient growth medium, which is a phenomenon akin to that of common fragile sites (CFSs). We aim to decipher the mechanism underlying the ‘fragility’ of this type of TNR region using methods that have been applied to our previous studies of CFSs [4-6].

The second research focus of our group is to analyse the proteins that are regulated by SUMOylation during the process of DNA replication. In particular, we are interested in proteins playing crucial roles when DNA replication is perturbed by either exogenous DNA replication stress, or endogenous difficulty caused by factors including long repeat regions, lacking of replication indication sites, or collisions with newly synthesized transcripts, etc. We have previously identified a panel of proteins SUMOylated when cells are under DNA replication stress [7]. We are currently characterizing the functional role of some of these proteins using molecular, genetic, and cell biological methods.

Figure: An example of the FRAXA locus (green; indicated by a yellow arrow) that is broken away from X chromosome detected on metaphase chromosome spreads (blue) by fluorescence in situ hybridization (FISH) analysis.


  1. C.T. McMurray, Mechanisms of trinucleotide repeat instability during human development, Nature reviews. Genetics, 11 (2010) 786-799.
  2. Y.H. Fu, D.P. Kuhl, A. Pizzuti, M. Pieretti, J.S. Sutcliffe, S. Richards, A.J. Verkerk, J.J. Holden, R.G. Fenwick, Jr., S.T. Warren, et al., Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox, Cell, 67 (1991) 1047-1058.
  3. R.R. Sinden, V.N. Potaman, E.A. Oussatcheva, C.E. Pearson, Y.L. Lyubchenko, L.S. Shlyakhtenko, Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA, Journal of biosciences, 27 (2002) 53-65.
  4. K.L. Chan, T. Palmai-Pallag, S. Ying, I.D. Hickson, Replication stress induces sister-chromatid bridging at fragile site loci in mitosis, Nature cell biology, 11 (2009) 753-760.
  5. Y. Liu, C.F. Nielsen, Q. Yao, I.D. Hickson, The origins and processing of ultra fine anaphase DNA bridges, Current opinion in genetics & development, 26 (2014) 1-5.
  6. S. Ying, S. Minocherhomji, K.L. Chan, T. Palmai-Pallag, W.K. Chu, T. Wass, H.W. Mankouri, Y. Liu, I.D. Hickson, MUS81 promotes common fragile site expression, Nature cell biology, 15 (2013) 1001-1007.
  7. S. Bursomanno, P. Beli, A.M. Khan, S. Minocherhomji, S.A. Wagner, S. Bekker-Jensen, N. Mailand, C. Choudhary, I.D. Hickson, Y. Liu, Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells, DNA repair, 25 (2015) 84-96.