Genomic instability and carcinogenesis

Genomic instability is a hallmark of human cancer. But how does genomic instability develop and impact the initiation and progression of cancer? And does it provide opportunities for therapeutic intervention? We study two causes of genomic instability, both related to perturbed DNA replication: (1) loss of DNA mismatch repair (MMR) leading to increased mutagenesis, and (2) defective G1/S control causing unscheduled S-phase entry, replication stress and DNA breakage. We develop novel gene modification tools to study genomic instability in cell culture and mouse models.

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