scholarly journals Histone H2A insufficiency causes chromosomal segregation defects due to anaphase chromosome bridge formation at rDNA repeats in fission yeast

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Takaharu G. Yamamoto ◽  
Da-Qiao Ding ◽  
Yuki Nagahama ◽  
Yuji Chikashige ◽  
Tokuko Haraguchi ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Histone H2a ◽  
Bridge Formation ◽  
Chromosomal Segregation ◽  
Chromosome Bridge

scholarly journals Histone H2A Phosphorylation Controls Crb2 Recruitment at DNA Breaks, Maintains Checkpoint Arrest, and Influences DNA Repair in Fission Yeast

2004 ◽  
Vol 24 (14) ◽  
pp. 6215-6230 ◽  
Author(s):  
Toru M. Nakamura ◽  
Li-Lin Du ◽  
Christophe Redon ◽  
Paul Russell
Keyword(s):  
Dna Repair ◽  
Fission Yeast ◽  
Large Scale ◽  
Dna Helicase ◽  
Histone H2a ◽  
Dna Breaks ◽  
Histone H2ax ◽  
Wide Range ◽  
Carboxy Terminal ◽  
Damaged Dna

ABSTRACT Mammalian ATR and ATM checkpoint kinases modulate chromatin structures near DNA breaks by phosphorylating a serine residue in the carboxy-terminal tail SQE motif of histone H2AX. Histone H2A is similarly regulated in Saccharomyces cerevisiae. The phosphorylated forms of H2AX and H2A, known as γ-H2AX and γ-H2A, are thought to be important for DNA repair, although their evolutionarily conserved roles are unknown. Here, we investigate γ-H2A in the fission yeast Schizosaccharomyces pombe. We show that formation of γ-H2A redundantly requires the ATR/ATM-related kinases Rad3 and Tel1. Mutation of the SQE motif to AQE (H2A-AQE) in the two histone H2A genes caused sensitivity to a wide range of genotoxic agents, increased spontaneous DNA damage, and impaired checkpoint maintenance. The H2A-AQE mutations displayed a striking synergistic interaction with rad22Δ (Rad52 homolog) in ionizing radiation (IR) survival. These phenotypes correlated with defective phosphorylation of the checkpoint proteins Crb2 and Chk1 and a failure to recruit large amounts of Crb2 to damaged DNA. Surprisingly, the H2A-AQE mutations substantially suppressed the IR hypersensitivity of crb2Δ cells by a mechanism that required the RecQ-like DNA helicase Rqh1. We propose that γ-H2A modulates checkpoint and DNA repair through large-scale recruitment of Crb2 to damaged DNA. This function correlates with evidence that γ-H2AX regulates recruitment of several BRCA1 carboxyl terminus domain-containing proteins (NBS1, 53BP1, MDC1/NFBD1, and BRCA1) in mammals.

Analysis of a histone H2A variant from fission yeast: evidence for a role in chromosome stability

1994 ◽  
Vol 245 (5) ◽  
pp. 628-635 ◽  
Author(s):  
A. M. Carr ◽  
S. M. Dorrington ◽  
J. Hindley ◽  
G. A. Phear ◽  
S. J. Aves ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Chromosome Stability ◽  
Histone H2a

scholarly journals Organization, primary structure, and evolution of histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe.

1985 ◽  
Vol 5 (11) ◽  
pp. 3261-3269 ◽  
Author(s):  
J Choe ◽  
T Schuster ◽  
M Grunstein
Keyword(s):  
Amino Acid ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Dna Sequences ◽  
Sequence Evolution ◽  
Hydrophobic Core ◽  
Histone H2a ◽  
Acid Protein ◽  
Close Proximity ◽  
Pair Sequence

The histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe were cloned and sequenced. Southern blot and sequence analyses showed that, unlike other eucaryotes, Saccharomyces cerevisiae included, S. pombe has unequal numbers of these genes, containing two histone H2A genes (H2A-alpha and -beta) and only one H2B gene (H2B-alpha) per haploid genome. H2A- and H2B-alpha are adjacent to each other and are divergently transcribed. H2A-beta has no other histone gene in close proximity. Preceding both H2A-alpha and -beta is a highly conserved 19-base-pair sequence (5'-CATCAC/AAACCCTAACCCTG-3'). The H2A DNA sequences encode two histone H2A subtypes differing in amino acid sequence (three residues) and size (H2A-alpha, 131 residues; H2A-beta, 130 residues). H2B-alpha codes for a 125-amino-acid protein. Sequence evolution is extensive between S. pombe and S. cerevisiae and displays unique patterns of divergence. Certain N-terminal sequences normally divergent between eucaryotes are conserved between the two yeasts. In contrast, the normally conserved hydrophobic core of H2A is as divergent between the yeasts as between S. pombe and calf.

scholarly journals Effects of the microtubule nucleator Mto1 on chromosomal movement, DNA repair, and sister chromatid cohesion in fission yeast

2019 ◽  
Vol 30 (21) ◽  
pp. 2695-2708 ◽  
Author(s):  
Jacob Zhurinsky ◽  
Silvia Salas-Pino ◽  
Ana B. Iglesias-Romero ◽  
Antonio Torres-Mendez ◽  
Benjamin Knapp ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fission Yeast ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Cytoplasmic Factor ◽  
Chromosomal Segregation ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Cohesin Subunit

Although the function of microtubules (MTs) in chromosomal segregation during mitosis is well characterized, much less is known about the role of MTs in chromosomal functions during interphase. In the fission yeast Schizosaccharomyces pombe, dynamic cytoplasmic MT bundles move chromosomes in an oscillatory manner during interphase via linkages through the nuclear envelope (NE) at the spindle pole body (SPB) and other sites. Mto1 is a cytoplasmic factor that mediates the nucleation and attachment of cytoplasmic MTs to the nucleus. Here, we test the function of these cytoplasmic MTs and Mto1 on DNA repair and recombination during interphase. We find that mto1Δ cells exhibit defects in DNA repair and homologous recombination (HR) and abnormal DNA repair factory dynamics. In these cells, sister chromatids are not properly paired, and binding of Rad21 cohesin subunit along chromosomal arms is reduced. Our findings suggest a model in which cytoplasmic MTs and Mto1 facilitate efficient DNA repair and HR by promoting dynamic chromosomal organization and cohesion in the nucleus.

Organization, primary structure, and evolution of histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe

1985 ◽  
Vol 5 (11) ◽  
pp. 3261-3269
Author(s):  
J Choe ◽  
T Schuster ◽  
M Grunstein
Keyword(s):  
Amino Acid ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Dna Sequences ◽  
Sequence Evolution ◽  
Hydrophobic Core ◽  
Histone H2a ◽  
Acid Protein ◽  
Close Proximity ◽  
Pair Sequence

The histone H2A and H2B genes of the fission yeast Schizosaccharomyces pombe were cloned and sequenced. Southern blot and sequence analyses showed that, unlike other eucaryotes, Saccharomyces cerevisiae included, S. pombe has unequal numbers of these genes, containing two histone H2A genes (H2A-alpha and -beta) and only one H2B gene (H2B-alpha) per haploid genome. H2A- and H2B-alpha are adjacent to each other and are divergently transcribed. H2A-beta has no other histone gene in close proximity. Preceding both H2A-alpha and -beta is a highly conserved 19-base-pair sequence (5'-CATCAC/AAACCCTAACCCTG-3'). The H2A DNA sequences encode two histone H2A subtypes differing in amino acid sequence (three residues) and size (H2A-alpha, 131 residues; H2A-beta, 130 residues). H2B-alpha codes for a 125-amino-acid protein. Sequence evolution is extensive between S. pombe and S. cerevisiae and displays unique patterns of divergence. Certain N-terminal sequences normally divergent between eucaryotes are conserved between the two yeasts. In contrast, the normally conserved hydrophobic core of H2A is as divergent between the yeasts as between S. pombe and calf.

scholarly journals Meiotic analyses show adaptations to maintenance of fertility in X1Y1X2Y2X3Y3X4Y4X5Y5 system of amazon frog Leptodactylus pentadactylus (Laurenti, 1768)

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Renata Coelho Rodrigues Noronha ◽  
Bruno Rafael Ribeiro de Almeida ◽  
Marlyson Jeremias Rodrigues da Costa ◽  
Cleusa Yoshiko Nagamachi ◽  
Cesar Martins ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Double Strand Breaks ◽  
Histone H2a ◽  
Terminal Portion ◽  
Late Pachytene ◽  
Strand Breaks ◽  
Chromosomal Segregation ◽  
Sexual Determination ◽  
Meiotic Analyses ◽  
Meiotic Cycle

Abstract Heterozygous chromosomal rearrangements can result in failures during the meiotic cycle and the apoptosis of germline, making carrier individuals infertile. The Amazon frog Leptodactylus pentadactylus has a meiotic multivalent, composed of 12 sex chromosomes. The mechanisms by which this multi-chromosome system maintains fertility in males of this species remain undetermined. In this study we investigated the meiotic behavior of this multivalent to understand how synapse, recombination and epigenetic modifications contribute to maintaining fertility and chromosomal sexual determination in this species. Our sample had 2n = 22, with a ring formed by ten chromosomes in meiosis, indicating a new system of sex determination for this species (X1Y1X2Y2X3Y3X4Y4X5Y5). Synapsis occurs in the homologous terminal portion of the chromosomes, while part of the heterologous interstitial regions performed synaptic adjustment. The multivalent center remains asynaptic until the end of pachytene, with interlocks, gaps and rich-chromatin in histone H2A phosphorylation at serine 139 (γH2AX), suggesting transcriptional silence. In late pachytene, paired regions show repair of double strand-breaks (DSBs) with RAD51 homolog 1 (Rad51). These findings suggest that Rad51 persistence creates positive feedback at the pachytene checkpoint, allowing meiosis I to progress normally. Additionally, histone H3 trimethylation at lysine 27 in the pericentromeric heterochromatin of this anuran can suppress recombination in this region, preventing failed chromosomal segregation. Taken together, these results indicate that these meiotic adaptations are required for maintenance of fertility in L. pentadactylus.

scholarly journals Mechanisms Generating Cancer Genome Complexity From A Single Cell Division Error

2019 ◽  
Author(s):  
Neil T. Umbreit ◽  
Cheng-Zhong Zhang ◽  
Luke D. Lynch ◽  
Logan J. Blaine ◽  
Anna M. Cheng ◽  
...  
Keyword(s):  
Genome Instability ◽  
Chromosome Breakage ◽  
Epigenetic Mark ◽  
Clonal Heterogeneity ◽  
Bridge Formation ◽  
Genome Complexity ◽  
Cancer Genomes ◽  
Chromosome Bridge ◽  
Bfb Cycle ◽  
Mutational Process

ABSTRACTThe chromosome breakage-fusion-bridge (BFB) cycle is a mutational process that produces gene amplification and genome instability. Signatures of BFB cycles can be observed in cancer genomes with chromothripsis, another catastrophic mutational process. Here, we explain this association by identifying a mutational cascade downstream of chromosome bridge formation that generates increasing amounts of chromothripsis. We uncover a new role for actomyosin forces in bridge breakage and mutagenesis. Chromothripsis then accumulates starting with aberrant interphase replication of bridge DNA, followed by an unexpected burst of mitotic DNA replication, generating extensive DNA damage. Bridge formation also disrupts the centromeric epigenetic mark, leading to micronucleus formation that itself promotes chromothripsis. We show that this mutational cascade generates the continuing evolution and sub-clonal heterogeneity characteristic of many human cancers.

Phosphorylation of H2A by Bub1 Prevents Chromosomal Instability Through Localizing Shugoshin

Science ◽  
2009 ◽  
Vol 327 (5962) ◽  
pp. 172-177 ◽  
Author(s):  
Shigehiro A. Kawashima ◽  
Yuya Yamagishi ◽  
Takashi Honda ◽  
Kei-ichiro Ishiguro ◽  
Yoshinori Watanabe
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Histone H2a

Bub1 is a multi-task protein kinase required for proper chromosome segregation in eukaryotes. Impairment of Bub1 in humans may lead to chromosomal instability (CIN) or tumorigenesis. Yet, the primary cellular substrate of Bub1 has remained elusive. Here, we show that Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast Schizosaccharomyces pombe. The h2a-SA mutant, in which all cellular H2A-S121 is replaced by alanine, phenocopies the bub1 kinase-dead mutant (bub1-KD) in losing the centromeric localization of shugoshin proteins. Artificial tethering of shugoshin to centromeres largely restores the h2a-SA or bub1-KD–related CIN defects, a function that is evolutionally conserved. Thus, Bub1 kinase creates a mark for shugoshin localization and the correct partitioning of chromosomes.

scholarly journals Cooperative Control of Crb2 by ATM Family and Cdc2 Kinases Is Essential for the DNA Damage Checkpoint in Fission Yeast

2005 ◽  
Vol 25 (24) ◽  
pp. 10721-10730 ◽  
Author(s):  
Toru M. Nakamura ◽  
Bettina A. Moser ◽  
Li-Lin Du ◽  
Paul Russell
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Cooperative Control ◽  
Genetic Interaction ◽  
Phosphorylation Site ◽  
Dna Damage Checkpoint ◽  
Histone H2a ◽  
Histone H4 ◽  
Checkpoint Response ◽  
Kinase Phosphorylation

ABSTRACT The cellular responses to double-stranded breaks (DSBs) typically involve the extensive accumulation of checkpoint proteins in chromatin surrounding the damaged DNA. One well-characterized example involves the checkpoint protein Crb2 in the fission yeast Schizosaccharomyces pombe. The accumulation of Crb2 at DSBs requires the C-terminal phosphorylation of histone H2A (known as γ-H2A) by ATM family kinases in chromatin surrounding the break. It also requires the constitutive methylation of histone H4 on lysine-20 (K20). Interestingly, neither type of histone modification is essential for the Crb2-dependent checkpoint response. However, H4-K20 methylation is essential in a crb2-T215A strain that lacks a cyclin-dependent kinase phosphorylation site in Crb2. Here we explain this genetic interaction by describing a previously overlooked effect of the crb2-T215A mutation. We show that crb2-T215A cells are able to initiate but not sustain a checkpoint response. We also report that γ-H2A is essential for the DNA damage checkpoint in crb2-T215A cells. Importantly, we show that inactivation of Cdc2 in γ-H2A-defective cells impairs Crb2-dependent signaling to the checkpoint kinase Chk1. These findings demonstrate that full Crb2 activity requires phosphorylation of threonine-215 by Cdc2. This regulation of Crb2 is independent of the histone modifications that are required for the hyperaccumulation of Crb2 at DSBs.

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