Sasaki Group • Laboratory of Gene Quantity Biology::National Institute of Genetics

Sasaki Group • Laboratory of Gene Quantity Biology

Molecular mechanisms and functions of extrachromosomal circular DNAs in eukaryotes

Faculty

SASAKI, Mariko

Associate Professor

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Lab HP

Research Summary

Eukaryotic cells encode genetic information on linear chromosomes. However, cancer cells often accumulate extrachromosomal circular DNAs that are derived from chromosomes. Having proto-oncogenes and drug-resistant genes, these circular DNAs are thought to drive the onset and progression of tumorigenesis and confer resistance to chemotherapy. Furthermore, different types of circular DNAs have been observed in normal human cells as well as in other organisms but their biological significance remains unclear. In our laboratory, we aim to understand molecular mechanisms underlying formation of various extrachromosomal circular DNAs and their functions.

(A) Gene amplification occurs on the chromosome or via extrachromosomal circular DNAs that are derived from a chromosome. (B) A colon adenocarcinoma cell line, COLO 320DM, accumulates extrachromosomal circular DNAs (arrows) that contain a proto-oncogene, c-myc.

Selected Publications

Sasaki M, Kobayashi T. Regulatory processes that maintain or alter ribosomal DNA stability during the repair of programmed DNA double-strand breaks. Genes Genet Syst. 2023 Sep 30;98(3):103-119.

Sasaki M, Kobayashi T. Ctf4 Prevents Genome Rearrangements by Suppressing DNA Double-Strand Break Formation and Its End Resection at Arrested Replication Forks. Mol Cell. 2017 May 18;66(4):533-545.e5.

Yokoyama M, Sasaki M, Kobayashi T. Spt4 promotes cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters. Cell Rep. 2023 Jan 31;42(1):111944.