Premium
Break‐induced replication links microsatellite expansion to complex genome rearrangements
Author(s) -
Leffak Michael
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.201700025
Subject(s) - trinucleotide repeat expansion , genome instability , microsatellite , microsatellite instability , biology , dna replication , genetics , genome , dna repair , dna , human genome , computational biology , dna damage , gene , allele
The instability of microsatellite DNA repeats is responsible for at least 40 neurodegenerative diseases. Recently, Mirkin and co‐workers presented a novel mechanism for microsatellite expansions based on break‐induced replication (BIR) at sites of microsatellite‐induced replication stalling and fork collapse. The BIR model aims to explain single‐step, large expansions of CAG/CTG trinucleotide repeats in dividing cells. BIR has been characterized extensively in Saccharomyces cerevisiae as a mechanism to repair broken DNA replication forks (single‐ended DSBs) and degraded telomeric DNA. However, the structural footprints of BIR‐like DSB repair have been recognized in human genomic instability and tied to the etiology of diverse developmental diseases; thus, the implications of the paper by Kim et al. (Kim JC, Harris ST, Dinter T, Shah KA, et al., Nat Struct Mol Biol 24: 55–60) extend beyond trinucleotide repeat expansion in yeast and microsatellite instability in human neurological disorders. Significantly, insight into BIR‐like repair can explain certain pathways of complex genome rearrangements (CGRs) initiated at non‐B form microsatellite DNA in human cancers.