Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression

Wang, Junhua; Pluth, Janice M.; Cooper, Priscilla K.; Cowan, Morton J.; Chen, David J.; Yannone, Steven M.

doi:10.1016/j.dnarep.2005.02.001

Cited by 95 publications

(97 citation statements)

References 52 publications

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“…Subsets of NHEJ may involve other factors such as Artemis (Moshous et al, 2001;Jeggo and O'Neill, 2002). The extent to which Artemis is required during canonical NHEJ (independent of V(D)J recombination) remains uncertain, as conflicting data on its requirement for end joining have been reported (Rooney et al, 2003;Riballo et al, 2004;Zhang et al, 2004;Wang et al, 2005b). However, Lig4 and Xrcc4 are essential for NHEJ and embryonic survival (Barnes et al, 1998;Frank et al, 1998;Gao et al, 1998b), and their interaction is required for efficient end joining as Lig4 is not sufficient to complete repair in the absence of Xrcc4 (Critchlow et al, 1997;Grawunder et al, 1997Grawunder et al, , 1998aBassing and Alt, 2004).…”

Section: Introductionmentioning

confidence: 99%

DNA double-strand break repair and development

Phillips

McKinnon

2007

Oncogene

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Normal development of an organism requires the ability to respond to DNA damage. A particularly deleterious lesion is a DNA double-strand break (DSB). The cellular response to DNA DSBs occurs via an integrated sensing and signaling network that maintains genomic stability. The outcomes of defective DNA DSB repair are related to the developmental stage of an organism, and often show striking tissue specificity. Many human diseases are associated with deficiencies in DNA DSB repair and can be characterized by neuropathology, immune deficiency, growth retardation or predisposition to cancer. This review will focus on the requirements of the DNA DSB response that function to maintain homeostasis during mammalian development.

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Section: Introductionmentioning

confidence: 99%

DNA double-strand break repair and development

Phillips

McKinnon

2007

Oncogene

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“…However, mutation of all phosphorylation sites in the Artemis gene did not result in diminished activity, whereas DNA-PK autophosphorylation was shown to be required for Artemis activation (Goodarzi et al, 2006). Although the types of lesions that need Artemis mediated processing have not yet been identified, it is clear that a subset of 15-20% of ionizing radiation-induced DSBs remain unrepaired for several days in Artemis deficient cells (Riballo et al, 2004;Wang et al, 2005;Darroudi et al, 2007).…”

Section: Processing Factors For Nhejmentioning

confidence: 99%

Non-homologous end-joining, a sticky affair

2007

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Rejoining of broken chromosomes is crucial for cell survival and prevention of malignant transformation. Most mammalian cells rely primarily on the non-homologous end-joining pathway of DNA double-strand break (DSB) repair to accomplish this task. This review focuses both on the core non-homologous end-joining machinery, which consists of DNA-dependent protein kinase and the ligase IV/XRCC4 complex, and on accessory factors that facilitate rejoining of a subset of the DSBs. We discuss how the ATM protein kinase and the Mre11/Rad50/Nbs1 complex might function in DSB repair and what role ionizing radiation-induced foci may play in this process.

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“…The three-dimensional structure of several RNA-specific b-CASP members has recently revealed the general organization of these proteins into two domains: a metallo-b-lactamase domain and a b-CASP domain, with the active site being located at the interface between the two domains (Ishikawa et al, 2006;Mandel et al, 2006). Several Serine residues, mostly located in the C-terminus half of the protein, have been identified in vitro and in vivo as targets of phosphatidylinositol 3-kinase like kinases, including DNA-PKcs (Poinsignon et al, 2004a; Riballo et al, 2004;Zhang et al, 2004;Chen et al, 2005;Ma et al, 2005;Wang et al, 2005b;Goodarzi et al, 2006;Soubeyrand et al, 2006). Unexpectedly however, Artemis function in V(D)J recombination does not rely upon the phosphorylation of these sites.…”

Section: Artemismentioning

confidence: 99%

“…The DDR is orchestrated by a series of biochemical events among which protein phosphorylation by the phosphatidylinositol 3-kinase like kinases , ATM and ATR, play a central role (for a review, see Sancar et al, 2004). Like many DNA repair factors, Artemis is hyperphosphorylated in an ATM-dependent manner after IR (Poinsignon et al, 2004a;Riballo et al, 2004;Zhang et al, 2004;Chen et al, 2005;Ma et al, 2005;Wang et al, 2005b;Goodarzi et al, 2006;Geng et al, 2007). The exact role of ATM-dependent phosphorylation of Artemis during DNA repair is not fully understood as mutations of the phosphorylation sites do not impact on the capacity of these Artemis mutants to complement the radiosensitivity of Artemis-deficient fibroblasts (Poinsignon et al, 2004a).…”

Section: Artemismentioning

confidence: 99%

“…Although it is clear that Artemis-deficient cells arrest normally in G1 following IR, the maintenance and/or recovery from the G2/M checkpoint following IR was found altered (Zhang et al, 2004;Wang et al, 2005b;Deckbar et al, 2007;Krempler et al, 2007). Whether this reflects a direct function of Artemis on cell cycle through the regulation of Cdk1-cyclin B (Zhang et al, 2004) or the impaired repair of a subset of damage after IR Krempler et al, 2007) remains an open issue.…”

Section: Artemismentioning

confidence: 99%

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V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining

et al. 2007

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The immune system is the site of intense DNA damage/ modification, which occur during the development and maturation of B and T lymphocytes. V(D)J recombination is initiated by the Rag1 and Rag2 proteins and the formation of a DNA double-strand break (DNA dsb). This DNA lesion is repaired through the use of the nonhomologous end-joining (NHEJ) pathway, several factors of which have been identified through the survey of immunodeficient conditions in humans and mice. Upon antigenic recognition in secondary lymphoid organs, mature B cells further diversify their repertoire through class switch recombination (CSR). CSR is a region-specific rearrangement process triggered by the activation-induced cytidine deaminase factor and also proceeds through the introduction of DNA dsb. However, unlike V(D)J recombination, CSR does not rely strictly on NHEJ for the repair of the DNA lesion. Instead, CSR, but not V(D)J recombination, requires the major factors of the DNA damage response. V(D)J recombination and CSR thus represent an interesting paradigm to study the regulation among the various DNA repair pathways. Oncogene (2007) 26, 7780-7791; doi:10.1038/sj.onc.1210875 Keywords: V(D)J recombination; class switch recombination; SCID; Artemis; Cernunnos; NHEJ V(D)J recombination and CSR: two rearrangement processes that shape the immune system repertoire B and T lymphocytes respond to foreign pathogens through specialized antigenic receptors, the B-cell receptor and T-cell receptor, respectively. The required diversity of these receptors is ensured by the V(D)J recombination process (Figure 1) which assembles previously scattered Variable (V), Diversity (D) and Joining (J) encoding gene segments through a specialized somatic DNA rearrangement mechanism (Tonegawa, 1983). The reaction is initiated by the lymphoid-specific factors, Rag1 and Rag2, which recognize recombination signal sequences (RSS) that flank all V, D and J gene units and introduce a DNA dsb at the border of the RSS (see Dudley et al. (2005) for a review on V(D)J recombination). The resulting DNA double-strand break (DNA dsb) is resolved by the ubiquitous DNA repair machinery known as non-homologous end-joining (NHEJ). The convergent efforts of scientists in the immunology and DNA repair fields were decisive in defining the various actors and molecular mechanisms of this DNA repair pathway over the years as will be discussed below.The terminal maturation of B lymphocytes, which occurs in germinal centres of secondary lymphoid organs upon antigen recognition, is accompanied by two additional molecular processing of immunoglobulin genes that increase the efficiency of the humoral response: (1) the class switch recombination (CSR, Figure 2) exchanges the immunoglobulin (Ig) constant region (CH), thus modifying the function of the Ig without altering its antigenic specificity (Manis et al., 2002b) and (2) somatic hypermutations are introduced in the Ig variable domains, thus increasing their affinity for antigen (Papavasiliou and Schatz, 2002). These two events ar...

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Artemis deficiency confers a DNA double-strand break repair defect and Artemis phosphorylation status is altered by DNA damage and cell cycle progression

Cited by 95 publications

References 52 publications

DNA double-strand break repair and development

DNA double-strand break repair and development

Non-homologous end-joining, a sticky affair

V(D)J and immunoglobulin class switch recombinations: a paradigm to study the regulation of DNA end-joining

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