Abstract

Centromeres are the complex structures responsible for the proper segregation of chromosomes during cell division. Structural or functional alterations of the centromere cause aneuploidies and other chromosomal aberrations that can induce cell death with consequences on health and survival of the organism as a whole. Because of their essential function in the cell, centromeres have evolved high flexibility and mechanisms of tolerance to preserve their function following stress, whether it is originating from within or outside the cell. Here, we review the main epigenetic mechanisms of centromeres’ adaptability to preserve their functional stability, with particular reference to neocentromeres and holocentromeres. The centromere position can shift in response to altered chromosome structures, but how and why neocentromeres appear in a given chromosome region are still open questions. Models of neocentromere formation developed during the last few years will be hereby discussed. Moreover, we will discuss the evolutionary significance of diffuse centromeres (holocentromeres) in organisms such as nematodes. Despite the differences in DNA sequences, protein composition and centromere size, all of these diverse centromere structures promote efficient chromosome segregation, balancing genome stability and adaptability, and ensuring faithful genome inheritance at each cellular generation.

Highlights

  • Centromeres are specialized chromatin regions that establish the assembly site for the kinetochore, a complex protein structure that mediates the attachment of spindle microtubules to chromosomes, permitting proper chromosome segregation during cell division

  • This process is extensively regulated by preloading complexes [24,25,26,27] containing accessory factors; specific chaperons for centromeric protein A (CENP-A), for instance in human cells identified as HJURP [29,30] and in Drosophila as Cal1 [20,31,32]; and cell cycle-dependent phosphoregulation

  • The centromere, complex used this function, has segregation ofTherefore chromosomes during cell adivision is structure essential for thefor survival of the cell adapted during evolution to respond to changes in the cellular microenvironment as well to those in and the whole organism

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Summary

Introduction

Centromeres are specialized chromatin regions that establish the assembly site for the kinetochore, a complex protein structure that mediates the attachment of spindle microtubules to chromosomes, permitting proper chromosome segregation during cell division. In S. pombe on the other hand, CENP-A homolog is incorporated during G2 [23] This process is extensively regulated by preloading complexes [24,25,26,27] (reviewed in [28]) containing accessory factors; specific chaperons for CENP-A, for instance in human cells identified as HJURP [29,30] and in Drosophila as Cal1 [20,31,32]; and cell cycle-dependent phosphoregulation (reviewed in [33]). The ubiquitylated old CENP-A is recognized by HJURP that favors a new ubiquitylated CENP-A deposition in a heterodimerization-dependent manner This allows centromere spatial positioning and epigenetic inheritance [36,37] (reviewed in [38]). Recent works have shown the centromeric presence of mobile elements, retrotransposons, in several species including Drosophila, [41,42], humans [43] and maize [44], probably contribute to the establishment and maintenance of eukaryotic centromeres while promoting their variability (reviewed in [45,46])

Centromere Flexibility in Response to Stress
Schematic
Neocentromere as a Functional and Evolutionary
Holocentromere
Conclusions
Full Text
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