Phosphorylation of Artemis following irradiation‐induced DNA damage

Poinsignon, Catherine; Chasseval, Régina de; Soubeyrand, Sébastien; Moshous, Despina; Fischer, Alain; Haché, Robert J.G.; Villartay, Jean‐Pierre de

doi:10.1002/eji.200425455

Cited by 57 publications

(65 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, we have found that mice with combined deficiency for Artemis and ATM are viable, with some living up to at least 9 months. In this regard, recent studies suggest that Artemis may, in fact, be epistatic to ATM in the IR-induced ATM signaling pathway (47,57,58). The viability of Artemis͞ATM double-deficient mice suggests that synergistic function of DNA-PKcs with ATM in preventing embryonic lethality does not involve Artemis.…”

Section: Discussionmentioning

confidence: 99%

Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development

Rooney

Alt

Sekiguchi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Assembly of Ig genes in B lineage cells involves two distinct DNA rearrangements. In early B cell development, site-specific double strand breaks (DSBs) at germ-line V, D, and J gene segments are joined via nonhomologous end-joining (NHEJ) to form variable region exons. Activated mature B cells can change expressed Ig heavy chain constant region exons by class switch recombination (CSR), which also involves DSB intermediates. Absence of any known NHEJ factor severely impairs joining of cleaved V, D, and J segments. In NHEJ, DNA-dependent protein kinase (DNA-PK), which is comprised of the Ku70͞80 end-binding heterodimer and the catalytic subunit (DNA-PKcs), activates Artemis to generate a nuclease that processes DSBs before ligation. Because inactivation of DNA-PKcs components also severely affects CSR, we tested whether DNA-PK also functions in CSR via activation of Artemis. To obviate the requirement for V(D)J recombination, we generated DNA-PKcs-and Artemis-deficient B cells that harbored preassembled Ig heavy chain and -light chain ''knock-in'' (HL) alleles. We found that Artemis-deficient HL B cells undergo robust CSR, indicating that DNA-PKcs functions in CSR via an Artemis-independent mechanism. To further elucidate potential Artemis-independent functions of DNA-PKcs, we asked whether the embryonic lethality associated with double-deficiency for DNA-PKcs and the related ataxia-telangiectasia-mutated (ATM) kinase was also observed in mice doubly deficient for ATM and Artemis. We found that ATM͞Artemis double-deficient mice were viable and born in normal Mendelian numbers. Therefore, we conclude that DNA-PKcs has Artemis-independent functions in CSR and normal development.ATM ͉ DNA-PKcs P recursor B and T cells assemble antigen receptor genes from component, germ-line V, D, and J segments via V(D)J recombination (1). V(D)J recombination is initiated by the lymphoid-specific RAG1͞2 endonuclease (RAG), which introduces DNA double strand breaks (DSBs) between V(D)J coding sequences and f lanking recombination signal (RS) sequences. RAG cleavage generates two distinct intermediates: hairpin coding ends and blunt RS ends, which are then fused via the nonhomologous end-joining (NHEJ) pathway of DSB repair (2). There are six known mammalian NHEJ factors (2).

show abstract

Section: Discussionmentioning

confidence: 99%

Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development

Rooney

Alt

Sekiguchi

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Additionally, Artemis is an ATM phosphorylation target [12,[22][23][24]. The model proposed is that ATM is required for Artemis-dependent end-processing and hence Artemis-dependent DSB repair [12].…”

Section: Apoptosismentioning

confidence: 99%

Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability

2006

View full text Add to dashboard Cite

Article (Unspecified) http://sro.sussex.ac.uk Jeggo, P. A. and Lobrich, M. (2006) Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair, 5 (9-10). pp. 1192 -1198 . ISSN 1568 This version is available from Sussex Research Online: http://sro.sussex.ac.uk/587/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. DNA damage response mechanisms encompass pathways of DNA repair, cell cycle checkpoint arrest and apoptosis. Together, these mechanisms function to maintain genomic stability in the face of exogenous and endogenous DNA damage. ATM is activated in response to double strand breaks and initiates cell cycle checkpoint arrest. Recent studies in human fibroblasts have shown that ATM also regulates a mechanism of end-processing that is required for a component of double strand break repair. Human fibroblasts rarely undergo apoptosis after ionising radiation and, therefore, apoptosis is not considered in our review. The dual function of ATM raises the question as to how the two processes, DNA repair and checkpoint arrest, interplay to maintain genomic stability. In this review, we consider the impact of ATM's repair and checkpoint functions to the maintenance of genomic stability following irradiation in G2. We discuss evidence that ATM's repair function plays little role in the maintenance of genomic stability following exposure to ionising radiation. ATM's checkpoint function has a bigger impact on genomic stability but strikingly the two damage response pathways co-operate in a more than additive manner. In contrast, ATM's repair function is important for survival post irradiation.Introduction.

show abstract

“…DNA-PKcs-dependent phosphorylation sites in the C-terminal portion of the Artemis have been suggested to have an important regulatory role in the activity of the protein (31), most of them not being SQ or TQ consensus DNA-PKcs sites (31). In addition, an ATM-and ATR-dependent phosphorylation of Artemis has been reported in cells (34,36,37,38), but its relation to Artemis function in DSB repair is not yet fully understood. Moreover, Artemis could have another role in the regulation of cell cycle progression following DNA damage, including UV irradiation (35,38), although this cell cycle function was not confirmed by others (39).…”

mentioning

confidence: 99%

Interplay between Ku, Artemis, and the DNA-dependent Protein Kinase Catalytic Subunit at DNA Ends

Drouet

Frit

Delteil

et al. 2006

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Phosphorylation of Artemis following irradiation‐induced DNA damage

Cited by 57 publications

References 32 publications

Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development

Artemis-independent functions of DNA-dependent protein kinase in Ig heavy chain class switch recombination and development

Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability

Interplay between Ku, Artemis, and the DNA-dependent Protein Kinase Catalytic Subunit at DNA Ends

Contact Info

Product

Resources

About