Motoko Unoki

Kyushu UniversityJapan

When I was an undergraduate student, I studied genetics of Carassius auratus langsdorfii (a Japanese crucian carp) which prospers by gynogenesis. Then I had studied carcinogenesis during my Ph.D course at the University of Tokyo, and continued the study at NCI in the US, and at RIKEN as a postdoc fellow for 11 years until I moved to Kyushu University as an assistant professor in 2010 (I was promoted to an associate professor in 2019). During the time, I identified UHRF1 as a novel methyl-CpG binding protein (Unoki et al., Oncogene, 2004). This finding contributed to open a door for clarifying molecular mechanism of maintenance DNA methylation by the DNMT1/UHRF1 complex. At Kyushu University, I discovered a novel histone modification “lysyl-hydroxylation” (Unoki et al., J. Biol. Chem., 2013), and also found that UHRF1 is partially involved in de novo DNA methylation during oocyte growth (Maenohara, Unoki et al., PLoS Genet., 2017). In 2015, I supported our Ph.D. student to identify CDCA7 and HELLS as causative genes for immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, which shows hypomethylation at centromer and pericentromere of chromosomes, by exome analysis (Thijssen et al., Nat. Commun., 2015). Currently, I’m trying to clarify functions of CDCA7 and HELLS. So far, I found that CDCA7 and HELLS are involved in non-homologous recombination (NHEJ) by facilitating access of Ku80 to DNA damage sites (Unoki et al., J. Clin., Invest., 2019). I also found that CDCA7 facilitates access of the DNMT1/UHRF1 complex to nascent DNA, and aberrant transcription from hypomethylated pericentromeric repeats in ICF patients causes R-loop formation, resulting in DNA damages (Unoki et al., Sci Rep., 2020). These findings are helpful for deepening the insights into mechanism of maintenance of DNA methylation and chromosome stability. In the future, I would like to contribute to care patients who suffer cancer and immunodeficiency by utilizing the knowledge which I have obtained.

2chapters authored