MUS81 promotes common fragile site expression

Ying, Songmin, Minocherhomji, Sheroy, Chan, Kok Lung , Palmai-Pallag, Timea, Chu, Wai Kit, Wass, Theresa, Mankouri, Hocine W., Liu, Ying and Hickson, Ian D. (2013) MUS81 promotes common fragile site expression. Nature Cell Biology, 15 (8). pp. 1001-1007. ISSN 1465-7392

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Fragile sites are chromosomal loci with a propensity to form gaps or breaks during early mitosis, and their instability is implicated as being causative in certain neurological disorders and cancers. Recent work has demonstrated that the so-called common fragile sites (CFSs) often impair the faithful disjunction of sister chromatids in mitosis. However, the mechanisms by which CFSs express their fragility, and the cellular factors required to suppress CFS instability, remain largely undefined. Here, we report that the DNA structure-specific nuclease MUS81-EME1 localizes to CFS loci in early mitotic cells, and promotes the cytological appearance of characteristic gaps or breaks observed at CFSs in metaphase chromosomes. These data indicate that CFS breakage is an active, MUS81-EME1-dependent process, and not a result of inadvertent chromatid rupturing during chromosome condensation. Moreover, CFS cleavage by MUS81-EME1 promotes faithful sister chromatid disjunction. Our findings challenge the prevailing view that CFS breakage is a nonspecific process that is detrimental to cells, and indicate that CFS cleavage actually promotes genome stability.

Keywords:MUS81, common fragile site, EME1, FANCD2, DNA replication, genome stability
Subjects:C Biological Sciences > C440 Molecular Genetics
C Biological Sciences > C130 Cell Biology
Divisions:College of Science > School of Life Sciences
ID Code:16000
Deposited On:14 Nov 2014 08:46

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