Re-replication of a Centromere Induces Chromosomal Instability and Aneuploidy

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The stable inheritance of genetic information requires an elaborate mitotic machinery that acts on the centromeres of chromosomes to ensure their precise segregation. Errors in this segregation can lead to aneuploidy, an unbalanced chromosomal state in which some chromosomes have different copy number than others. Because aneuploidy is associated with developmental abnormalities and diseases such as cancer, there is considerable interest in understanding how these segregation errors arise. Much of this interest has focused on identifying defects in proteins that make up the mitotic machinery. Here, we show that defects in a completely separate process, the control of DNA replication initiation, can lead to chromosome segregation errors as a result of inappropriate re-replication of centromeres. Similar deregulation of replication initiation proteins has been observed in primary human tumors and shown to promote oncogenesis in mouse models. Together, these results raise the possibility that centromeric re-replication may be an additional source of aneuploidy in cancer. In combination with our previous work showing that re-replication is a potent inducer of gene amplification, these results also highlight the versatility of re-replication as a source of genomic instability.

Vyšlo v časopise: Re-replication of a Centromere Induces Chromosomal Instability and Aneuploidy. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005039
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005039

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