Kyushu University Academic Staff Educational and Research Activities Database
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Kawasoe Yoshitaka Last modified date:2021.10.12

Assistant Professor / Integrative Biology
Department of Biology
Faculty of Sciences


Graduate School
Undergraduate School


Homepage
http://www.biology.kyushu-u.ac.jp/~chromosome/
The laboratory of Chromosome Biology .
Academic Degree
Ph. D. (Dr. of Science)
Country of degree conferring institution (Overseas)
No
Field of Specialization
Molecular biology, biochemistry (DNA repair, replication)
ORCID(Open Researcher and Contributor ID)
0000-0003-0925-2004
Total Priod of education and research career in the foreign country
00years00months
Research
Research Interests
  • The analysis of the mechanism of mismatch repair coupled with DNA replication
    keyword : DNA repair, mismatch repair, PCNA, Xenopus egg extracts, in vitro reconstitution
    2010.04.
  • The regulation of PCNA dynamics by the mismatch repair system
    keyword : PCNA unloading, mismatch repair, DNA replication, Xenopus egg extracts, in vitro reconstitution
    2017.04.
  • A biochemical analysis that the mismatch repair system improves the fidelity of DNA double strand break repair
    keyword : homologous recombination, mismatch repair, Xenopus egg extracts, in vitro reconstitution
    2017.04.
Academic Activities
Papers
1. Yoshitaka Kawasoe, Toshiki Tsurimoto, Takuro Nakagawa, Hisao Masukata, Tatsuro S. Takahashi, MutSα maintains the mismatch repair capability by inhibiting PCNA unloading., eLife, 10.7554/eLife.15155, 5, 2016JULY, 2016.07, [URL], Eukaryotic mismatch repair (MMR) utilizes single-strand breaks as signals to target the strand to be repaired. DNA-bound PCNA is also presumed to direct MMR. The MMR capability must be limited to a post-replicative temporal window during which the signals are available. However, both identity of the signal(s) involved in the retention of this temporal window and the mechanism that maintains the MMR capability after DNA synthesis remain unclear. Using Xenopus egg extracts, we discovered a mechanism that ensures long-term retention of the MMR capability. We show that DNA-bound PCNA induces strand-specific MMR in the absence of strand discontinuities. Strikingly, MutS a inhibited PCNA unloading through its PCNA-interacting motif, thereby extending significantly the temporal window permissive to strand-specific MMR. Our data identify DNA-bound PCNA as the signal that enables strand discrimination after the disappearance of strand discontinuities, and uncover a novel role of MutS a in the retention of the post-replicative MMR capability..
2. Atsuhiro Shimada, Yoshitaka Kawasoe, Yoshito Hata, Tatsuro S. Takahashi, Ryoji Masui, Seiki Kuramitsu, Kenji Fukui, MutS stimulates the endonuclease activity of MutL in an ATP-hydrolysis-dependent manner, FEBS JOURNAL, 10.1111/febs.12344, 280, 14, 3467-3479, 2013.07, [URL], In the initial steps of DNA mismatch repair, MutS recognizes a mismatched base and recruits the latent endonuclease MutL onto the mismatch-containing DNA in concert with other proteins. MutL then cleaves the error-containing strand to introduce an entry point for the downstream excision reaction. Because MutL has no intrinsic ability to recognize a mismatch and discriminate between newly synthesized and template strands, the endonuclease activity of MutL is strictly regulated by ATP-binding in order to avoid nonspecific degradation of the genomic DNA. However, the activation mechanism for its endonuclease activity remains unclear. In this study, we found that the coexistence of a mismatch, ATP and MutS unlocks the ATP-binding-dependent suppression of MutL endonuclease activity. Interestingly, ATPase-deficient mutants of MutS were unable to activate MutL. Furthermore, wild-type MutS activated ATPase-deficient mutants of MutL less efficiently than wild-type MutL. We concluded that ATP hydrolysis by MutS and MutL is involved in the mismatch-dependent activation of MutL endonuclease activity..
3. Niyo Kato, Yoshitaka Kawasoe, Hannah Williams, Elena Coates, Upasana Roy, Yuqian Shi, Lorena S. Beese, Orlando D. Scharer, Hong Yan, Max E. Gottesman, Tatsuro S. Takahashi, Jean Gautier, Sensing and Processing of DNA Interstrand Crosslinks by the Mismatch Repair Pathway, CELL REPORTS, 10.1016/j.celrep.2017.10.032, 21, 5, 1375-1385, 2017.10, [URL], DNA interstrand crosslinks (ICLs) that are repaired in non-dividing cells must be recognized independently of replication-associated DNA unwinding. Using cell-free extracts from Xenopus eggs that support neither replication nor transcription, we establish that ICLs are recognized and processed by the mismatch repair (MMR) machinery. We find that ICL repair requires MutS alpha (MSH2-MSH6) and the mismatch recognition FXE motif in MSH6, strongly suggesting that MutS alpha functions as an ICL sensor. MutS alpha recruits MutL alpha and EXO1 to ICL lesions, and the catalytic activity of both these nucleases is essential for ICL repair. As anticipated for a DNA unwinding-independent recognition process, we demonstrate that least distorting ICLs fail to be recognized and repaired by the MMR machinery. This establishes that ICL structure is a critical determinant of repair efficiency outside of DNA replication..
4. Riki Terui, Koji Nagao, Yoshitaka Kawasoe, Kanae Taki, Torahiko L. Higashi, Seiji Tanaka, Takuro Nakagawa, Chikashi Obuse, Hisao Masukata, Tatsuro S. Takahashi, Nucleosomes around a mismatched base pair are excluded via an Msh2-dependent reaction with the aid of SNF2 family ATPase Smarcad1, Genes and Development, 10.1101/gad.310995.117, 32, 11-12, 806-821, 2018.06, [URL], Post-replicative correction of replication errors by the mismatch repair (MMR) system is critical for suppression of mutations. Although the MMR system may need to handle nucleosomes at the site of chromatin replication, how MMR occurs in the chromatin environment remains unclear. Here, we show that nucleosomes are excluded from a >1-kb region surrounding a mismatched base pair in Xenopus egg extracts. The exclusion was dependent on the Msh2–Msh6 mismatch recognition complex but not the Mlh1-containing MutL homologs and counteracts both the HIRA- and CAF-1 (chromatin assembly factor 1)-mediated chromatin assembly pathways. We further found that the Smarcad1 chromatin remodeling ATPase is recruited to mismatch-carrying DNA in an Msh2-dependent but Mlh1-independent manner to assist nucleosome exclusion and that Smarcad1 facilitates the repair of mismatches when nucleosomes are preassembled on DNA. In budding yeast, deletion of FUN30, the homolog of Smarcad1, showed a synergistic increase of spontaneous mutations in combination with MSH6 or MSH3 deletion but no significant increase with MSH2 deletion. Genetic analyses also suggested that the function of Fun30 in MMR is to counteract CAF-1. Our study uncovers that the eukaryotic MMR system has an ability to exclude local nucleosomes and identifies Smarcad1/Fun30 as an accessory factor for the MMR reaction..
5. Mathew J K Jones, Camille Gelot, Stephanie Munk, Amnon Koren, Yoshitaka Kawasoe, Kelly A George, Ruth E Santos, Jesper V Olsen, Steven A McCarroll, Mark G Frattini, Tatsuro S Takahashi, Prasad V Jallepalli, Human DDK rescues stalled forks and counteracts checkpoint inhibition at unfired origins to complete DNA replication., Molecular cell, 10.1016/j.molcel.2021.01.004, 81, 3, 426-441, 2021.02, [URL], Eukaryotic genomes replicate via spatially and temporally regulated origin firing. Cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) promote origin firing, whereas the S phase checkpoint limits firing to prevent nucleotide and RPA exhaustion. We used chemical genetics to interrogate human DDK with maximum precision, dissect its relationship with the S phase checkpoint, and identify DDK substrates. We show that DDK inhibition (DDKi) leads to graded suppression of origin firing and fork arrest. S phase checkpoint inhibition rescued origin firing in DDKi cells and DDK-depleted Xenopus egg extracts. DDKi also impairs RPA loading, nascent-strand protection, and fork restart. Via quantitative phosphoproteomics, we identify the BRCA1-associated (BRCA1-A) complex subunit MERIT40 and the cohesin accessory subunit PDS5B as DDK effectors in fork protection and restart. Phosphorylation neutralizes autoinhibition mediated by intrinsically disordered regions in both substrates. Our results reveal mechanisms through which DDK controls the duplication of large vertebrate genomes..
Presentations
1. The Elg1-RFC complex is the major PCNA unloader in Xenopus egg extracts
.
2. The Elg1‒RFC2‒5 complex (Elg1‒RFC) is the major PCNA‒unloading complex in Xenopus egg extracts.
3. Yoshitaka Kawasoe, Sakiko Shimokawa, Toshiki Tsurimoto and Tatsuro Takahashi, The Elg1-Rfc2–5 complex (Elg1-RFC) is the major PCNA-unloading complex in Xenopus egg extracts, 岡崎フラグメント—不連続DNA 複製モデル 50周年記念国際シンポジウム, 2018.12.
4. Yoshitaka Kawasoe, Toshiki Tsurimoto, Takuro Nakagawa, Hisao Masukata and Tatsuro Takahashi, MutSα prevents dissociation of PCNA from DNA to keep strand information for eukaryotic mismatch repair, 3R Symposium, 2014.11.
5. MutSα prevents dissociation of PCNA from DNA to keep strand information for eukaryotic mismatch repair.
6. Yoshitaka Kawasoe, Toshiki Tsurimoto, Takuro Nakagawa, Hisao Masukata and Tatsuro Takahashi, Evidence that DNA-loaded PCNA acts as the strand marker for eukaryotic mismatch repair, Cold Spring Harbor Laboratory Meeting 2013, EUKARYOTIC DNA REPLICATION & GENOME MAINTENANCE, 2013.09.
7. 河添好孝, Orientation of PCNA loading determines the strand specificity of the eukaryotic mismatch repair reaction, National Tsing Hua University‐Osaka University Life Science Student Activity Fair 2013 Student Symposium, 2013.05.
8. PCNA is a molecular determinant for the strand specificity in eukaryotic mismatch repair.
9. PCNA plays a key role in identification of the newly synthesized DNA strand in eukaryotic mismatch repair.
Membership in Academic Society
  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN
Educational
Educational Activities
I mainly teach students attending school of sciences and graduate school of systems life sciences in our laboratory. I also teach practical courses for undergraduate students.