Centromere innovations within a mouse species.
Document Type
Article
Publication Date
11-17-2023
Original Citation
Gambogi C,
Pandey N,
Dawicki-McKenna J,
Arora U,
Liskovykh M,
Ma J,
Lamelza P,
Larionov V,
Lampson M,
Logsdon G,
Dumont B,
Black B.
Centromere innovations within a mouse species. Sci Adv. 2023;9(46):eadi5764.
Keywords
JMG, Mice, Animals, Chromosomal Proteins, Non-Histone, Autoantigens, Centromere, Centromere Protein A, Nucleosomes, Mammals
JAX Source
Sci Adv. 2023;9(46):eadi5764.
ISSN
2375-2548
PMID
37967185
DOI
https://doi.org/10.1126/sciadv.adi5764
Grant
This work was supported by NIH grants GM130302 (B.E.B.), GM108360 (J.M.D.-M.), K99 GM147352 (G.A.L.), GM133415 (B.L.D.), F31 CA268727 (U.P.A.), and a Basser Center for BRCA Early Career Award (N.P.).
Abstract
Mammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive and rapidly evolving DNA. We focused on a mouse species, Mus pahari, that we found has evolved to house centromere-specifying centromere protein-A (CENP-A) nucleosomes at the nexus of a satellite repeat that we identified and termed π-satellite (π-sat), a small number of recruitment sites for CENP-B, and short stretches of perfect telomere repeats. One M. pahari chromosome, however, houses a radically divergent centromere har- boring ~6 mega–base pairs of a homogenized π-sat–related repeat, π-satB, that contains >20,000 functional CENP-B boxes. There, CENP-B abundance promotes accumulation of microtubule-binding components of the kinetochore and a microtubule-destabilizing kinesin of the inner centromere. We propose that the balance of pro- and anti-microtubule binding by the new centromere is what permits it to segregate during cell division with high fidelity alongside the older ones whose sequence creates a markedly different molecular composition.