Gross Chromosomal Rearrangement at Centromeres

被引：1
作者：
Xu, Ran [1 ,2 ]
Pan, Ziyi [1 ,2 ]
Nakagawa, Takuro [1 ,2 ]
机构：
[1] Osaka Univ, Grad Sch Sci, Dept Biol Sci, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
[2] Osaka Univ, Forefront Res Ctr, Grad Sch Sci, 1-1 Machikaneyama, Toyonaka, Osaka 5600043, Japan
来源：
BIOMOLECULES | 2024年 / 14卷 / 01期
关键词：
centromere; DNA repeat; heterochromatin; CENP-A; DNA recombination; DNA repair; gross chromosomal rearrangement; fission yeast; humans; isochromosome; DOUBLE-STRAND BREAKS; H3; LYSINE-9; METHYLATION; REPLICATION PROTEIN-A; DNA-DAMAGE RESPONSE; CENP-A; HOMOLOGOUS RECOMBINATION; HISTONE H3; FISSION YEAST; MITOTIC RECOMBINATION; RAD54; PROTEIN;
D O I：
10.3390/biom14010028
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Centromeres play essential roles in the faithful segregation of chromosomes. CENP-A, the centromere-specific histone H3 variant, and heterochromatin characterized by di- or tri-methylation of histone H3 9th lysine (H3K9) are the hallmarks of centromere chromatin. Contrary to the epigenetic marks, DNA sequences underlying the centromere region of chromosomes are not well conserved through evolution. However, centromeres consist of repetitive sequences in many eukaryotes, including animals, plants, and a subset of fungi, including fission yeast. Advances in long-read sequencing techniques have uncovered the complete sequence of human centromeres containing more than thousands of alpha satellite repeats and other types of repetitive sequences. Not only tandem but also inverted repeats are present at a centromere. DNA recombination between centromere repeats can result in gross chromosomal rearrangement (GCR), such as translocation and isochromosome formation. CENP-A chromatin and heterochromatin suppress the centromeric GCR. The key player of homologous recombination, Rad51, safeguards centromere integrity through conservative noncrossover recombination between centromere repeats. In contrast to Rad51-dependent recombination, Rad52-mediated single-strand annealing (SSA) and microhomology-mediated end-joining (MMEJ) lead to centromeric GCR. This review summarizes recent findings on the role of centromere and recombination proteins in maintaining centromere integrity and discusses how GCR occurs at centromeres.
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