Literature DB >> 29986897

Micronuclei Formation Is Prevented by Aurora B-Mediated Exclusion of HP1a from Late-Segregating Chromatin in Drosophila.

Brandt Warecki1, William Sullivan2.   

Abstract

While it is known that micronuclei pose a serious risk to genomic integrity by undergoing chromothripsis, mechanisms preventing micronucleus formation remain poorly understood. Here, we investigate how late-segregating acentric chromosomes that would otherwise form micronuclei instead reintegrate into daughter nuclei by passing through Aurora B kinase-dependent channels in the nuclear envelope of Drosophila melanogaster neuroblasts. We find that localized concentrations of Aurora B preferentially phosphorylate H3(S10) on acentrics and their associated DNA tethers. This phosphorylation event prevents HP1a from associating with heterochromatin and results in localized inhibition of nuclear envelope reassembly on endonuclease- and X-irradiation-induced acentrics, promoting channel formation. Finally, we find that HP1a also specifies initiation sites of nuclear envelope reassembly on undamaged chromatin. Taken together, these results demonstrate that Aurora B-mediated regulation of HP1a-chromatin interaction plays a key role in maintaining genome integrity by locally preventing nuclear envelope assembly and facilitating the incorporation of late-segregating acentrics into daughter nuclei.
Copyright © 2018 by the Genetics Society of America.

Entities:  

Keywords:  acentric; genome integrity; micronuclei; nuclear envelope

Mesh:

Substances:

Year:  2018        PMID: 29986897      PMCID: PMC6116970          DOI: 10.1534/genetics.118.301031

Source DB:  PubMed          Journal:  Genetics        ISSN: 0016-6731            Impact factor:   4.562


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