Satellite DNAs and human sex chromosome variation

Čechová, Monika; Miga, Karen H.

doi:10.1016/j.semcdb.2022.04.022

Cited by 7 publications

(6 citation statements)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the DNA constituting the secondary constriction of some satellited chromosomes, turns out to be due to repeat expansions, as in FRAXA, ICF, etc. New sequencing and bioinformatic tools are only beginning to harness a full appreciation of these tandem repeats and their relationship to chromosome structure ( Cechova, 2020 ; Liehr, 2021 ; Suzuki and Morishita, 2021 ; Thakur et al, 2021 ; Altemose, 2022 ; Altemose et al, 2022 ; Cechova and Miga, 2022 ; Gall-Duncan et al, 2022 ; Hoyt et al, 2022 ; Nurk et al, 2022 ). This nomenclature, while not comprehensive, lacks clear boundaries.…”

Section: Fragile Sites and Repeatsmentioning

confidence: 99%

Fragile sites, chromosomal lesions, tandem repeats, and disease

Mirceta

Shum²,

Schmidt³

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites. Fragile sites cytogenetically manifest as localized gaps or discontinuities in chromosome structure and are an important genetic, biological, and health-related phenomena. Common fragile sites (∼230), present in most individuals, are induced by aphidicolin and can be associated with cancer; of the 27 molecularly-mapped common sites, none are associated with a particular DNA sequence motif. Rare fragile sites (≳ 40 known), ≤ 5% of the population (may be as few as a single individual), can be associated with neurodevelopmental disease. All 10 molecularly-mapped folate-sensitive fragile sites, the largest category of rare fragile sites, are caused by gene-specific CGG/CCG tandem repeat expansions that are aberrantly CpG methylated and include FRAXA, FRAXE, FRAXF, FRA2A, FRA7A, FRA10A, FRA11A, FRA11B, FRA12A, and FRA16A. The minisatellite-associated rare fragile sites, FRA10B, FRA16B, can be induced by AT-rich DNA-ligands or nucleotide analogs. Despiralized lesions and multi-branched inter-chromosomal associations at the heterochromatic satellite repeats of chromosomes 1, 9, 16 are inducible by de-methylating agents like 5-azadeoxycytidine and can spontaneously arise in patients with ICF syndrome (Immunodeficiency Centromeric instability and Facial anomalies) with mutations in genes regulating DNA methylation. ICF individuals have hypomethylated satellites I-III, alpha-satellites, and subtelomeric repeats. Ribosomal repeats and subtelomeric D4Z4 megasatellites/macrosatellites, are associated with chromosome location, fragility, and disease. Telomere repeats can also assume fragile sites. Dietary deficiencies of folate or vitamin B12, or drug insults are associated with megaloblastic and/or pernicious anemia, that display chromosomes with fragile sites. The recent discovery of many new tandem repeat expansion loci, with varied repeat motifs, where motif lengths can range from mono-nucleotides to megabase units, could be the molecular cause of new fragile sites, or other chromosomal lesions. This review focuses on repeat-associated fragility, covering their induction, cytogenetics, epigenetics, cell type specificity, genetic instability (repeat instability, micronuclei, deletions/rearrangements, and sister chromatid exchange), unusual heritability, disease association, and penetrance. Understanding tandem repeat-associated chromosomal fragile sites provides insight to chromosome structure, genome packaging, genetic instability, and disease.

show abstract

Section: Fragile Sites and Repeatsmentioning

confidence: 99%

Fragile sites, chromosomal lesions, tandem repeats, and disease

Mirceta

Shum²,

Schmidt³

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Isochromosomes whose arms are mirror images of each other are commonly found in cancer cells 15 . Isochromosomes of chr21 and chrX cause Down and Turner syndromes, respectively 16 , 17 . Compared to mammalian centromeres, the fission yeast S. pombe centromeres are short (35~110 kb) but contain inverted DNA repeats flanking a non-repetitive core sequence 18 , 19 .…”

Section: Introductionmentioning

confidence: 99%

Fission yeast Srr1 and Skb1 promote isochromosome formation at the centromere

et al. 2023

View full text Add to dashboard Cite

Rad51 maintains genome integrity, whereas Rad52 causes non-canonical homologous recombination leading to gross chromosomal rearrangements (GCRs). Here we find that fission yeast Srr1/Ber1 and Skb1/PRMT5 promote GCRs at centromeres. Genetic and physical analyses show that srr1 and skb1 mutations reduce isochromosome formation mediated by centromere inverted repeats. srr1 increases DNA damage sensitivity in rad51 cells but does not abolish checkpoint response, suggesting that Srr1 promotes Rad51-independent DNA repair. srr1 and rad52 additively, while skb1 and rad52 epistatically reduce GCRs. Unlike srr1 or rad52, skb1 does not increase damage sensitivity. Skb1 regulates cell morphology and cell cycle with Slf1 and Pom1, respectively, but neither Slf1 nor Pom1 causes GCRs. Mutating conserved residues in the arginine methyltransferase domain of Skb1 greatly reduces GCRs. These results suggest that, through arginine methylation, Skb1 forms aberrant DNA structures leading to Rad52-dependent GCRs. This study has uncovered roles for Srr1 and Skb1 in GCRs at centromeres.

show abstract

“…The mammalian Y chromosome is male-specific, with a genome size of about 60 Mb, half is a euchromatin region containing several genes, whereas the other half is a heterochromatic region consisting only of repeat sequences, DYZ1 and DYZ2 [Nakahori et al, 1986;Cechova and Miga, 2022]. The euchromatin region is divided into the pseudoautosomal regions (PARs), which are located at both ends of the Y chromosome and are thought to have a genome sequence that is almost identical to that of the X chromosome, and the malespecific region of the Y chromosome (MSY) [Skaletsky et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

Y Chromosome Genomic Variations and Biological Significance in Human Diseases and Health

Kuroki,

Fukami

2023

Cytogenet Genome Res

View full text Add to dashboard Cite

The Y chromosome is a haploid genome unique to males with no genes essential for life. It is easily transmitted to the next generation without being repaired by recombination, even if a major genomic structural alteration occurs. On the other hand, the Y chromosome genome is basically a genomic region transmitted only from father to son, reflecting a male-specific inheritance between generations. The Y chromosome exhibits genomic structural differences among different ethnic groups and individuals. The Y chromosome was previously thought to affect only male-specific phenotypes, but recent studies have revealed associations between the Y chromosomes and phenotypes common to both males and females, such as certain types of cancer and neuropsychiatric disorders. This evidence was discovered with the finding of the mosaic loss of the Y chromosome in somatic cells. This phenomenon is also affected by environmental factors, such as smoking and aging. In the past, functional analysis of the Y chromosome has been elucidated by assessing the function of Y chromosome-specific genes and the association between Y chromosome haplogroups and human phenotypes. These studies are currently being conducted intensively. Additionally, the recent advance of large-scale genome cohort studies has increased the amount of Y chromosome genomic information available for analysis, making it possible to conduct more precise studies of the relationship between genome structures and phenotypes. In this review, we will introduce recent analyses using large-scale genome cohort data and previously reported association studies between Y chromosome haplogroups and human phenotypes, such as male infertility, cancer, cardiovascular system traits, and neuropsychiatric disorders. The function and biological role of the Y chromosome in human phenotypes will also be discussed.

show abstract

Satellite DNAs and human sex chromosome variation

Cited by 7 publications

References 176 publications

Fragile sites, chromosomal lesions, tandem repeats, and disease

Fragile sites, chromosomal lesions, tandem repeats, and disease

Fission yeast Srr1 and Skb1 promote isochromosome formation at the centromere

Y Chromosome Genomic Variations and Biological Significance in Human Diseases and Health

Contact Info

Product

Resources

About