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ATM and RPA in meiotic chromosome synapsis and recombination

Plug, Annemieke W. and Peters, Antoine H. F. M. and Xu, Yang and Keegan, Kathleen S. and Hoekstra, Merl F. and Baltimore, David and de Boer, Peter and Ashley, Terry (1997) ATM and RPA in meiotic chromosome synapsis and recombination. Nature Genetics, 17 (4). pp. 457-461. ISSN 1061-4036. https://resolver.caltech.edu/CaltechAUTHORS:20200422-150958617

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Abstract

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 checkpoints. ATM also plays a role in meiosis. Spermatogenesis in Atm−/− male mice is disrupted, with chromosome fragmentation leading to meiotic arrest; 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 specialized structure along which meiotic recombination occurs. Recombination, preceded by pairing of homologous chromosomes, is thought to require heteroduplex formation between homologous DNA, followed by strand exchange. These early meiotic steps (entailing the formation and processing of meiotic recombination intermediates with DNA-strand interruptions) require ssDNA-binding proteins such as replication protein A (RPA; refs 5-7). In somatic cells, DNA damage induces ATM-dependent phosphorylation of RPA. We demonstrate here that ATM and RPA co-localize along synapsed meiotic chromosomes and at sites where interactions between ectopic homologous chromosome regions appear to initiate. In Atm−/− meiotic prophase sper-matocytes, immuno-localization shows that RPA is present along synapsing chromosomes and at sites of fragmentation of the SC. These results suggest that RPA and ATM co-localize at sites where interhomologous-DNA interactions occur during meiotic prophase and where breaks associated with meiotic recombination take place after synapsis, implying a possible functional interaction between these two proteins.


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https://doi.org/10.1038/ng1297-457DOIArticle
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ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1997 Nature Publishing Group. Received 18 July; accepted 20 October 1997. We thank P. Moens and B. Spyropoulos for anti-CORI antibodies; C. Radding, E. Golub and G. Reddy for the RAD5 I affinity-purified antiserum;]. Ingles for polyclonal antibody against RPA; Z.-Q. Pan for the monoclonal antibody against the 70-kD subunit of RPA; and D. Hill (Oncogene Research) for the ATMI antiserum. We also thank M.S. Meyn and C. H. Westphal for helpful discussions and comments. This project was supported by NIH grants (to T.A. and D. B.). D.B. is an American Cancer Society research professor and Y.X. was supported by a postdoctoral fellowship from the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation. The work of M.P.H. and K.S.K. was supported by ICOS Corporation.
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NIHUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Damon Runyon Cancer Research FoundationUNSPECIFIED
ICOS CorporationUNSPECIFIED
Issue or Number:4
Record Number:CaltechAUTHORS:20200422-150958617
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200422-150958617
Official Citation:Plug, A., Peters, A., Xu, Y. et al. ATM and RPA in meiotic chromosome synapsis and recombination. Nat Genet 17, 457–461 (1997). https://doi.org/10.1038/ng1297-457
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102726
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Apr 2020 19:45
Last Modified:23 Apr 2020 19:45

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