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Precarious maintenance of simple DNA repeats in eukaryotes
Author(s) -
Neil Alexander J.,
Kim Jane C.,
Mirkin Sergei M.
Publication year - 2017
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201700077
Subject(s) - biology , trinucleotide repeat expansion , telomere , genetics , dna replication , genome , dna repair , microsatellite , dna , replication timing , evolutionary biology , computational biology , gene , allele
In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break‐induced replication, lead to the deleterious large‐scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in maintaining functional repetitive regions of the genome such as telomeres and centromeres.