Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Expert Rev Mol Med. 2022 Sep 5;24:e32. doi: 10.1017/erm.2022.16.
Roughly 3% of the human genome consists of microsatellites or tracts of short tandem repeats (STRs). These STRs are often unstable, undergoing high-frequency expansions (increases) or contractions (decreases) in the number of repeat units. Some microsatellite instability (MSI) is seen at multiple STRs within a single cell and is associated with certain types of cancer. A second form of MSI is characterised by expansion of a single gene-specific STR and such expansions are responsible for a group of 40+ human genetic disorders known as the repeat expansion diseases (REDs). While the mismatch repair (MMR) pathway prevents genome-wide MSI, emerging evidence suggests that some MMR factors are directly involved in generating expansions in the REDs. Thus, MMR suppresses some forms of expansion while some MMR factors promote expansion in other contexts. This review will cover what is known about the paradoxical effect of MMR on microsatellite expansion in mammalian cells.
人类基因组约有 3%由微卫星或短串联重复序列 (STR) 组成。这些 STR 通常不稳定，会经历重复单位数量的高频扩展（增加）或收缩（减少）。某些微卫星不稳定性 (MSI) 可见于单个细胞内的多个 STR 中，与某些类型的癌症有关。第二种形式的 MSI 以单个基因特异性 STR 的扩展为特征，这种扩展是负责一组 40 多种人类遗传疾病的原因，称为重复扩展疾病 (REDs)。虽然错配修复 (MMR) 途径可防止全基因组 MSI，但新出现的证据表明，一些 MMR 因子直接参与 REDs 中扩展的产生。因此，MMR 抑制某些形式的扩展，而一些 MMR 因子在其他情况下促进扩展。这篇综述将涵盖关于 MMR 对哺乳动物细胞中微卫星扩展的矛盾影响的已知内容。
