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発表内容

Title:
Positive and negative regulation of DNA replication through G-quadruplexes

 

Speaker:
Hisao Masai
Tokyo Metropolitan Institute of Medical Science; E-mail: masai-hs(at)igakuken.or.jp

 

Abstract:
G-quadruplexes (G4s) appear in both DNA and RNA, and recent studies implicate these structures in various biological reactions including telomere regulation, epigenome regulation, transcription, translation, splicing, viral maintenance and functions, transpositions, repair and recombination. In this seminar I would like to introduce our recent studies on the roles of DNA replication.
Genome needs to replicate itself once and only once with minimum error in a given cell cycle. This task is hard to achieve, given the size of the genome, the time allotted, and various threats that could interfere with the process. Therefore, the rules of DNA replication may be fairly relaxed once cells make commitment to S phase. Indeed, origin choice appears to be stochastic even in yeasts with smaller genomes. Bacteria, in contrast, utilize a single, highly efficient origin for initiation. This is a very efficient mode of replication, but are more vulnerable to environmental changes. An alternative mode of replication of E. coli occurs on R-loops. R-loop formation is facilitated by the presence of multiple G-tracts, that can form G4 structure. The presence of G4-forming sequences near significant proportions of replication origins, identified through genome-wide analyses in higher eukaryotes including human, was noted. We are exploring now how these non-B DNA structures could be involved in potential mechanisms for relaxed modes of initiation of DNA replication.
The replication timing regulation involves suppression of origin firing by Rif1 which recognizes and binds to G4 on the chromosome. Timing regulation is not essential for completion of S phase, but may coordinate the replication process with other chromosome events including replication, epigenome regulation and DNA repair/ mutagenesis.
Thus, non-B DNA structures, such as G4 and RNA-DNA hybrid, now emerge as important genome signature that may contribute to robust and plastic nature of genome functions. I would like to discuss positive and negative regulation of DNA replication through G4 and its specific interacting proteins.

References:
1) Masai H et al. Annu Rev Biochem. 2010 79:89-130.
2) Matsumoto S et al. J Cell Biol. 2011 Oct 31;195(3):387-401.
3) Hayano M et al. Genes Dev. 2012 Jan 15;26(2):137-50.
4) Kanoh Y et al. Nat Struct Mol Biol. 2015 Nov;22(11):889-97.
5) Masai H et al. Sci Rep. 2019 Jun 13;9(1):8618.
6) Kobayashi S et al. Mol Cell Biol. 2019 Feb 4;39(4) pii: e00364-18.
7) Masai H et al. J Biol Chem. 2018 Nov 2;293(44):17033-17049.