Programmed <scp>DNA</scp> breaks in lymphoid cells: repair mechanisms and consequences in human disease

Procházková, Jana; Loizou, Joanna I.

doi:10.1111/imm.12547

Cited by 14 publications

(14 citation statements)

References 106 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Programmed DSBs are induced during meiosis, mating type switching in yeast, and V(D)J recombination and IgH class switch recombination in lymphoid cells (Haber 2012; Lam and Keeney 2015; Prochazkova and Loizou 2015). Outside of these contexts, causes of DNA DSBs can be classified into two broad categories: 1) toxic exposures and 2) failure of endogenous processes.…”

Section: Causes Of Dsbsmentioning

confidence: 99%

“…NHEJ is a conserved pathway to resolve the trauma of DNA DSBs and dysfunction in DSB repair can result in genome instability and human disease (Malkova and Haber 2012; McKinnon and Caldecott 2007; Pierce et al 2001; Prochazkova and Loizou 2015; Rulten and Caldecott 2013). In S. cerevisiae , c-NHEJ is a haploid specific process that occurs predominantly in G1.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

“…Failure to repair even a single DSB can lead to cell death, whereas misrepair can introduce catastrophic chromosomal translocations (Malkova and Haber 2012). Defects in DSB repair pathways are implicated in cancer and a number of congenital disorders, including primary immunodeficiency diseases (McKinnon and Caldecott 2007; Pierce et al 2001; Prochazkova and Loizou 2015; Rulten and Caldecott 2013). …”

mentioning

confidence: 99%

See 2 more Smart Citations

Consider the workhorse: Nonhomologous end-joining in budding yeast

Emerson

Bertuch

2016

Biochem. Cell Biol.

View full text Add to dashboard Cite

DNA double strand breaks (DSBs) are dangerous sources of genome instability and must be repaired by the cell. Nonhomologous end joining (NHEJ) is an evolutionarily conserved pathway to repair DSBs by direct ligation of the ends, with no requirement for a homologous template. While NHEJ is the primary DSB repair pathway in mammalian cells, conservation of the core NHEJ factors throughout eukaryotes make the pathway attractive for study in model organisms. The budding yeast, Saccharomyces cerevisiae, has been used extensively to develop a functional picture of NHEJ. In this review, we will discuss the current understanding of NHEJ in S. cerevisiae. Topics include canonical end-joining, alternative end-joining, and pathway regulation. Particular attention will be paid to the NHEJ mechanism involving core factors, including Yku70/80, Dnl4, Lif1, and Nej1, as well as the various factors implicated in the processing of the broken ends. The relevance of chromatin dynamics to NHEJ will also be discussed. This review illustrates the use of S. cerevisiae as a powerful system to understand the principles of NHEJ, as well as in pioneering the direction of the field.

show abstract

Section: Causes Of Dsbsmentioning

confidence: 99%

Section: Summary and Perspectivesmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Consider the workhorse: Nonhomologous end-joining in budding yeast

Emerson

Bertuch

2016

Biochem. Cell Biol.

View full text Add to dashboard Cite

show abstract

“…18 Defective genes of the recombination machinery including RAG1/2 induce severe combined immunodeficiencies. 19,20 The basis of T cell-dependent humoral immunity against foreign pathogens, and the ultimate expression of the adaptive immune response, is termed the germinal center (GC) reaction. 21,22 Germinal centers represent a unique collaboration between proliferating antigen-specific B cells, T-follicular helper cells, and the specialized follicular dendritic cells that constitutively occupy the central follicular zones of secondary lymphoid organs.…”

Section: T Cells Originate In the Thymus And Develop Into Cd8 + Cytotmentioning

confidence: 99%

Secondary immunodeficiency in lymphoproliferative malignancies

Friman

Winqvist

Blimark

et al. 2016

Hematological Oncology

View full text Add to dashboard Cite

Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease- and treatment-related factors. Supportive treatment, including early vaccination, anti-infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

“…More than twenty molecules are involved in the V(D) J recombination and CSR; and inability to persecute the programmed DDR results in primary immunodeficiency (PID) ( Table 1) [3,6,[8][9][10][11][12][13][14][15]. The patients with defect either in DNA damage signal or in NHEJ process present PID phenotype, and often show one or more of phenotypes that include radiosensitivity, predisposition to malignancy, developmental delay, and neurological deficits ( Table 2).…”

Section: Dna Damage Repair Networkmentioning

confidence: 99%

Recent advances in the study of immunodeficiency and DNA damage response

Morio

2017

Int J Hematol

View full text Add to dashboard Cite

DNA breaks can be induced by exogenous stimuli or by endogenous stress, but are also generated during recombination of V, D, and J genes (V(D)J recombination), immunoglobulin class switch recombination (CSR). Among various DNA breaks generated, DNA double strand break (DSB) is the most deleterious one. DNA damage response (DDR) is initiated when DSBs are detected, leading to DNA break repair by non-homologous end joining (NHEJ). The process is critically important for the generation of diversity for foreign antigens; and failure to exert DNA repair leads to immunodeficiency such as severe combined immunodeficiency and hyper-IgM syndrome. In V(D)J recombination, DSBs are induced by RAG1/2; and generated post-cleavage hairpins are resolved by Artemis/DNA-PKcs/KU70/KU80. DDR is initiated by ataxia-telangiectasia mutated as a master regulator together with MRE11/RAD50/NBS1 complex. Finally, DSBs are repaired by NHEJ. The defect of one of the molecules shows various degree of immunodeficiency and radiosensitivity. Upon CSR inducing signal, DSBs induced by activation-induced cytidine deaminase and endonucleases elicit DDR. Broken ends are repaired either by NHEJ or by mismatch repair system. Patients with radiosensitive SCID require hematopoietic cell transplantation as a curative therapy; but the procedures for eradication of recipient hematopoietic cells are often associated with severe toxicity.

show abstract

Programmed DNA breaks in lymphoid cells: repair mechanisms and consequences in human disease

Cited by 14 publications

References 106 publications

Consider the workhorse: Nonhomologous end-joining in budding yeast

Consider the workhorse: Nonhomologous end-joining in budding yeast

Secondary immunodeficiency in lymphoproliferative malignancies

Recent advances in the study of immunodeficiency and DNA damage response

Contact Info

Product

Resources

About