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近期对防止异位着丝粒形成机制的深入了解。

Recent insights into mechanisms preventing ectopic centromere formation.

机构信息

Department of Biology, New York University, New York, NY 10003-6688, USA.

出版信息

Open Biol. 2021 Sep;11(9):210189. doi: 10.1098/rsob.210189. Epub 2021 Sep 8.

DOI:10.1098/rsob.210189
PMID:34493071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8424319/
Abstract

The centromere is a specialized chromosomal structure essential for chromosome segregation. Centromere dysfunction leads to chromosome segregation errors and genome instability. In most eukaryotes, centromere identity is specified epigenetically by CENP-A, a centromere-specific histone H3 variant. CENP-A replaces histone H3 in centromeres, and nucleates the assembly of the kinetochore complex. Mislocalization of CENP-A to non-centromeric regions causes ectopic assembly of CENP-A chromatin, which has a devastating impact on chromosome segregation and has been linked to a variety of human cancers. How non-centromeric regions are protected from CENP-A misincorporation in normal cells is largely unexplored. Here, we review the most recent advances on the mechanisms underlying the prevention of ectopic centromere formation, and discuss the implications in human disease.

摘要

着丝粒是一种对染色体分离至关重要的染色体结构。着丝粒功能障碍会导致染色体分离错误和基因组不稳定。在大多数真核生物中，着丝粒的身份是由 CENP-A（一种着丝粒特异性组蛋白 H3 变体）通过表观遗传来指定的。CENP-A 取代着丝粒中的组蛋白 H3，并启动动粒复合物的组装。CENP-A 错误定位到非着丝粒区域会导致 CENP-A 染色质的异位组装，这对染色体分离有毁灭性的影响，并与多种人类癌症有关。在正常细胞中，非着丝粒区域如何免受 CENP-A 错误掺入的影响，在很大程度上尚不清楚。在这里，我们综述了最近在防止异位着丝粒形成的机制方面的进展，并讨论了其在人类疾病中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/470028bf9570/rsob210189f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/572700e20dd3/rsob210189f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/01c1b1be53e4/rsob210189f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/ea718829c16a/rsob210189f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/470028bf9570/rsob210189f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/572700e20dd3/rsob210189f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/01c1b1be53e4/rsob210189f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/ea718829c16a/rsob210189f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0316/8424319/470028bf9570/rsob210189f04.jpg

相似文献

[1]
Recent insights into mechanisms preventing ectopic centromere formation.

Open Biol. 2021-9

[2]
Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells.

Oncotarget. 2017-7-18

[3]
Guarding the Genome: CENP-A-Chromatin in Health and Cancer.

Genes (Basel). 2020-7-16

[4]
Ectopic centromere nucleation by CENP--a in fission yeast.

Genetics. 2014-12

[5]
Targeted De Novo Centromere Formation in Drosophila Reveals Plasticity and Maintenance Potential of CENP-A Chromatin.

Dev Cell. 2020-2-10

[6]
Centromeric and ectopic assembly of CENP-A chromatin in health and cancer: old marks and new tracks.

Nucleic Acids Res. 2019-2-20

[7]
A Genome-Wide Screen Reveals a Role for the HIR Histone Chaperone Complex in Preventing Mislocalization of Budding Yeast CENP-A.

Genetics. 2018-7-16

[8]
Heterochromatin and RNAi regulate centromeres by protecting CENP-A from ubiquitin-mediated degradation.

PLoS Genet. 2018-8-8

[9]
The ins and outs of CENP-A: Chromatin dynamics of the centromere-specific histone.

Semin Cell Dev Biol. 2023-2-15

[10]
In vitro centromere and kinetochore assembly on defined chromatin templates.

Nature. 2011-8-28

引用本文的文献

[1]
A dynamic population of prophase CENP-C is required for meiotic chromosome segregation.

PLoS Genet. 2023-11

[2]
Humanization reveals pervasive incompatibility of yeast and human kinetochore components.

G3 (Bethesda). 2023-12-29

[3]
Prenatally detected six duplications at Xp22.33-p11.22: a case report.

BMC Pregnancy Childbirth. 2023-4-27

[4]
Cell cycle control of kinetochore assembly.

Nucleus. 2022-12

本文引用的文献

[1]
CENP-A overexpression promotes distinct fates in human cells, depending on p53 status.

Commun Biol. 2021-3-26

[2]
Reduced gene dosage of histone H4 prevents CENP-A mislocalization and chromosomal instability in Saccharomyces cerevisiae.

Genetics. 2021-5-17

[3]
Centromeric chromatin integrity is compromised by loss of Cdk5rap2, a transcriptional activator of CENP-A.

Biomed Pharmacother. 2021-6

[4]
CENP-A overexpression promotes aneuploidy with karyotypic heterogeneity.

J Cell Biol. 2021-4-5

[5]
Induction of spontaneous human neocentromere formation and long-term maturation.

J Cell Biol. 2021-3-1

[6]
H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory.

J Cell Sci. 2020-7-24

[7]
The role of the histone H3 variant CENPA in prostate cancer.

J Biol Chem. 2020-6-19

[8]
Dbf4-Dependent Kinase (DDK)-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A in .

G3 (Bethesda). 2020-6-1

[9]
Structural basis for centromere maintenance by Drosophila CENP-A chaperone CAL1.

EMBO J. 2020-3-5

[10]
Centromere chromatin structure - Lessons from neocentromeres.

Exp Cell Res. 2020-2-8

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