ATM and RPA in meiotic chromosome synapsis and recombination

@article{Plug1997ATMAR,
  title={ATM and RPA in meiotic chromosome synapsis and recombination},
  author={Annemieke W. Plug and Antoine Hfm Peters and Yang Xu and Kathleen S. Keegan and Merl F. Hoekstra and David Baltimore and P. de Boer and Terry Ashley},
  journal={Nature Genetics},
  year={1997},
  volume={17},
  pages={457-461}
}
ATM is a member of the phosphatidylinositol 3-kinase (PIK)like kinases, some of which are active in regulating DNA damage-induced mitotic cell-cycle checkpoints1,2. ATM also plays a role in meiosis. Spermatogenesis in Atm−/− male mice is disrupted, with chromosome fragmentation leading to meiotic arrest3; in human patients with ataxia-telangiectasia (A-T), gonadal atrophy is common. Immuno-localization studies indicate that ATM is associated with sites along the synaptonemal complex (SC), the… Expand
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TLDR
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References

SHOWING 1-10 OF 24 REFERENCES
The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.
TLDR
This is the first demonstration of a nuclear association of Atr and Atm proteins with meiotic chromosomes and suggests a direct role for these proteins in recognizing and responding to DNA strand interruptions that occur during meiotic recombination. Expand
Meiosis-Specific DNA Double-Strand Breaks Are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family
TLDR
These findings strongly implicate Spo11 as the catalytic subunit of the meiotic DNA cleavage activity and provide direct evidence that the mechanism of meiotic recombination initiation is evolutionarily conserved. Expand
The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast.
TLDR
The results indicate a functional similarity between MEC1 and ATM, and suggest that RPA phosphorylation is involved in a conserved eukaryotic DNA damage-response pathway defective in A-T. Expand
Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.
TLDR
Findings indicate that the ATM gene product plays an essential role in a diverse group of cellular processes, including meiosis, the normal growth of somatic tissues, immune development, and tumor suppression. Expand
DMC1: A meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression
TLDR
DMC1 phenotypes provide further evidence that recombination and SC formation are interrelated processes and are consistent with a requirement for DNA-DNA interactions during SC formation, and additional evidence suggests that arrest occurs at a meiosis-specific cell cycle "checkpoint" in response to a primary defect in prophase chromosome metabolism. Expand
Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae
TLDR
In synchronous cultures of S. cerevisiae undergoing meiosis, an early event in the meiotic recombination pathway, site-specific double strand breaks (DSBs), occurs early in prophase, in some instances well before tripartite synaptonemal complex (SC) begins to form, supporting the view that events involving DSBs are required for SC formation. Expand
Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family.
  • M. Hoekstra
  • Biology, Medicine
  • Current opinion in genetics & development
  • 1997
TLDR
Recent studies in this protein kinase family indicate an important role for ATM and ATR in a meiotic surveillance mechanism that may regulate proper chromosome transmission. Expand
Presynaptic association of Rad51 protein with selected sites in meiotic chromatin.
TLDR
The time course of appearance of Rad51 association with chromatin, its distribution, and its interaction with other Rad5l-associated sequences suggests that it plays an important role preselection of sequences and synaptic initiation. Expand
Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein
TLDR
It is suggested that the Rad51 protein, probably together with Rad52 protein, is involved in a step to convert DSBs to the next intermediate in recombination. Expand
The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells.
TLDR
This is the first time that modification of a repair protein, RPA, has been linked with a DNA damage response and suggests that phosphorylation may play a role in regulating DNA repair pathways. Expand
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