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Break-induced replication

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Full-Text Articles in Molecular Biology

Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan Jan 2022

Instability And Extrachromosomal Circular Dna Formation At Microsatellites And Unstable Dna Sequences, Matilyn M. Shanahan

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We have previously documented our evidence of genetic instabilities at the (Pu/Py)78 and (ATTCT)47 sequences and our reasoning for identifying break-induced replication (BIR) as the mode of repair responsible for the mutations in the DNA flanking the unstable inserts. Now, as our lab investigates the protein mechanisms at play in the BIR pathway taking place at these sites, we are also expanding our knowledge of how this mechanism extends into the pathways responsible for forming extrachromosomal circular DNA (eccDNA) molecules. We have documented the phenomena posed as the driving factors for eccDNA formation in our systems containing (Pu/Py)78 and (ATTCT)47. …


Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada Jan 2022

Genomic Instability At A Polypurine/Polypyrimidine Repeat Sequence, Nathen S. Zavada

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Microsatellite repeat sequences have been shown to induce replication stalling, fork collapse, double-strand breaks (DSBs), and possibly stimulate break-induced replication. In this study we use a dual-fluorescent HeLa model that is designed to monitor recombination at an ectopic site through use of flow cytometry and inverse PCR with a microsatellite in the lagging strand for DNA synthesis. To test the stability of the 78 bp polypurine/pyrimidine repeat from the PDK1 locus, we subjected cells to replication stress drugs designed to induce DSBs and measure break-induced replication (BIR). The study revealed that polypurine repeat cells undergo endogenous stress contributing to instability …