A novel function of DNA repair molecule Nbs1 in terminal differentiation of the lens fibre cells and cataractogenesis

AbstractNeurons are the longest-living cells in our bodies, becoming post-mitotic in early development upon terminal differentiation. Their lack of DNA replication makes them reliant on DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, potentially giving rise to genomic dysfunction that may influence cognitive decline and neurodegenerative diseases. Despite this challenge, our knowledge of how genome instability emerges and what mechanisms neurons and other long-lived cells may have evolved to protect their genome integrity over the human life span is limited. Using a targeted sequencing approach, we demonstrate that neurons consolidate much of their DNA repair efforts into well-defined hotspots that protect genes that are essential for their identity and function. Our findings provide a basis to understand genome integrity as it relates to aging and disease in the nervous system.One Sentence SummaryRecurrent DNA repair hotspots in neurons are linked to genes essential for identity and function.

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Altered Fine Structure of B Lymphocytes Correlated with Defective Terminal Differentiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007237x ◽

1973 ◽

Vol 31 ◽

pp. 386-387

Author(s):

Dale E. Bockman ◽

L. Y. Frank Wu ◽

Alexander R. Lawton ◽

Max D. Cooper

Keyword(s):

Immune Deficiency ◽

B Lymphocytes ◽

Plasma Cells ◽

Present Report ◽

Specific Antigen ◽

Terminal Differentiation ◽

Second Stage ◽

Two Stages ◽

Deficiency Diseases ◽

Cell Line Generation

B-lymphocytes normally synthesize small amounts of immunoglobulin, some of which is incorporated into the cell membrane where it serves as receptor of antigen. These cells, on contact with specific antigen, proliferate and differentiate to plasma cells which synthesize and secrete large quantities of immunoglobulin. The two stages of differentiation of this cell line (generation of B-lymphocytes and antigen-driven maturation to plasma cells) are clearly separable during ontogeny and in some immune deficiency diseases. The present report describes morphologic aberrations of B-lymphocytes in two diseases in which second stage differentiation is defective.

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Paracrystalline Aggregates of Psoriatic Keratin and Their Relation to Normal Keratin Structure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120096 ◽

1985 ◽

Vol 43 ◽

pp. 680-681

Author(s):

S. Trachtenberg ◽

P.M. Steinert ◽

B.L. Trus ◽

A.C. Steven

Keyword(s):

Cell Death ◽

Stratum Corneum ◽

Intermediate Filament ◽

Skin Disease ◽

Amorphous Matrix ◽

Terminal Differentiation ◽

Proteolytic Degradation ◽

Horny Layer ◽

Chronic Skin ◽

Chronic Skin Disease

During terminal differentiation of vertebrate epidermis, certain specific keratin intermediate filament (KIF) proteins are produced. Keratinization of the epidermis involves cell death and disruption of the cytoplasm, leaving a network of KIF embedded in an amorphous matrix which forms the outer horny layer known as the stratum corneum. Eventually these cells are shed (desquamation). Normally, the processes of differentiation, keratinization, and desquamation are regulated in an orderly manner. In psoriasis, a chronic skin disease, a hyperkeratotic stratum corneum is produced, resulting in abnormal desquamation of unusually large scales. In this disease, the normal KIF proteins are diminished in amount or absent, and other proteins more typical of proliferative epidermal cells are present. There is also evidence of proteolytic degradation of the KIF.

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Ultrastructural features of prognostic significance in human oral cancer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123490 ◽

1992 ◽

Vol 50 (1) ◽

pp. 618-619

Author(s):

Karvita B. Ahluwalia ◽

Nidhi Sharma

Keyword(s):

Oral Cancer ◽

Squamous Cell ◽

Common Knowledge ◽

Prognostic Significance ◽

Growth Control ◽

Terminal Differentiation ◽

Squamous Cell Carcinomas ◽

Effective Therapy ◽

Invasive Potential ◽

Biological Behaviour

It is common knowledge that apparently similar tumors often show different responses to therapy. This experience has generated the idea that histologically similar tumors could have biologically distinct behaviour. The development of effective therapy therefore, has the explicit challenge of understanding biological behaviour of a tumor. The question is which parameters in a tumor could relate to its biological behaviour ? It is now recognised that the development of malignancy requires an alteration in the program of terminal differentiation in addition to aberrant growth control. In this study therefore, ultrastructural markers that relate to defective terminal differentiation and possibly invasive potential of cells have been identified in human oral leukoplakias, erythroleukoplakias and squamous cell carcinomas of the tongue.

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