Life Sciences | Medicine and Health Sciences Lynch syndrome (LS)
leads to an increased risk of early-onset colorectal and other
types of cancer and is caused by germline mutations in DNA
mismatch repair (MMR) genes. Loss of MMR function results in a
mutator phenotype that likely underlies its role in
tumorigenesis. However, loss of MMR also results in the
elimination of a DNA damage-induced checkpoint/apoptosis
activation barrier that may allow damaged cells to grow
unchecked. A fundamental question is whether loss of MMR
provides pre-cancerous stem cells an immediate selective
advantage in addition to establishing a mutator phenotype. To
test this hypothesis in an in vivo system, we utilized the
planarian Schmidtea mediterranea which contains a significant
population of identifiable adult stem cells. We identified a
planarian homolog of human MSH2, a MMR gene which is mutated in
38% of LS cases. The planarian Smed-msh2 is expressed in stem
cells and some progeny. We depleted Smed-msh2 mRNA levels by
RNA-inte