References

Uber Kataract in Vebindung mit Einer Eugntumliche Haut Degeneration. Cataracts in association with a peculiar degeneration of the skin. Arch Fur Ophthalmol 4 159-182, 1887. 2. MS Thomson. Poikiloderma Congenitale. Br J Dermatol 48 221-234, 1936. 3. A Carlton. Skin diseases and cataract. Br J Dermatol 55 83, 1943. 4. GB Sexton. Thomson's syndrome. Can Med Assoc J 70 662-665, 1954. 5. DG Starr, JP McClure, JM Connor. Non-dermatological complications and genetic aspects of the...

The Aging Locus

These results were interpreted as S1R4-42 strains having a longer life span, because S1R4-mediated transcriptional silencing is redirected from silenced mating-type loci and telomeres to an (at that time) unidentified aging locus (Fig. 2). This model is consistent with experiments that demonstrated a competition between HM loci and telomeres for recruitment of SIR proteins (28,29). The aging locus would define a third locus (or loci) with an affinity for SIR proteins. In young S1R4-42 cells,...

Caloric Restriction And Erc Formation

Caloric restriction has been shown to extend the life span in a wide number of organisms (68-71). Growth on low glucose has been used as a model for caloric restriction in yeast and was found to extend the life span (72,73). Yeast are normally grown in medium containing 2 glucose. Growth on 0.1 glucose results in a 55 extension of the median life span (72) growth on 0.5 glucose results in a more modest 24 extension in the life span (73). In yeast, glucose activates the cAMP-dependent protein...

Long Life Is Associated With Increased Resistance To Stress

A number of early studies on the long-lived (referred to as age) mutants focused on stress resistance. Long-lived mutants show increased resistance to oxidative stress, heat, and ultraviolet (UV) light (summarized in refs. 20 and 27). A summary of data showing correlations between mean longevity in a variety of mutant strains and subsequent life spans is shown in Figure 1. This information can be supplemented with studies from the Johnson laboratory that are available online (see http...

Dna Repair And Genomic Stability In Drosophila

Several dozen genes implicated in DNA repair, replication, recombination, and or cell cycle control have been identified in Drosophila by mutations that render larvae hypersensitive to mutagens 65,66 . Many more genes of this class are suggested by sequence homology and analysis of the Drosophila genomic sequence. A comprehensive list of Drosophila DNA repair genes has been made available by several investigators, at http www.dmrepair.ucdavis.edu 67 . With the interesting exception of...

Drosophila Aging And Genomic Stability

DNA damage and somatic mutation have long been hypothesized to be possible contributors to aging 90 . However, there have been relatively few studies directly linking aging and genomic stability in Drosophila. Aging Drosophila have been shown to accumulate the oxidatively damaged DNA base 8-oxo-gua-nine 6 . In addition, mitochondrial DNA mutations have been found to be more abundant in older flies 7 . Therefore, at least some types of DNA damage are accumulating in the aging Drosophila adult. A...

Biochemical Features Of The Recq4 Helicase

Structural Similarities to Other RecQ Helicase Family Members The RECQL4 helicase has a helicase domain that contains seven consensus motifs in the middle of the molecule see Fig. 2 . The amino acid sequence of the helicase domain is 40.8 homologous to that of the E. coli RecQ helicase, the prototype of this family, within the same range as the other four family members, RECQL, WRN, BLM, and RECQ5 helicases. Of the five human RecQ helicases, defective WRN, BLM, and RECQL4 helicases are...

Info

S., MacKay, J. F., Lagally, M. G., and Petrini, J. H. In situ visualization of DNA double-strand break repair in human fibroblasts. Science 280 590-592, 1998. Stewart, G. S., Maser, R. S., Stankovic, T., Bressan, D. A., Kaplan, M. I., Jaspers, N. G., Raams, A., Byrd, P. J., Petrini, J. H., and Taylor, A. M. The DNA doublestrand break repair gene hMRE11 is mutated in individuals with an ataxia-telang-iectasia-like disorder. Cell 99 577-587, 1999. Michelson, R. J. and...

Phenotype Of Atm Knockout Mice

Several different strains of Atm y mice have been generated since the cloning of the ATM gene 96,99,148 . The mice all have a similar AT-like phenotypes in that they express neurological abnormalities, immune defects, genetic instability, radiation sensitivity, infertility, and a high incidence of lymphoma. Despite these phenotypic similarities with AT patients, there are differences, including severe growth retardation, universal sterility, and death from lymphoma by age 6 months in Atm ' mice...

Function Of

Identification of proteins that interact with WRN has helped to shed light on the in vivo functions of WRNp. Some laboratories have characterized the association of WRN with specific candidate interacting proteins, whereas others have screened cDNA libraries by the yeast two-hybrid system, isolated the WRN complex from the cell extracts, or captured the interacting proteins by binding to a WRNp affinity column. Interestingly, each method identified different sets of WRN-interact-ing proteins....

Structural Chromosomal Aberrations

Translocations, Chromosomal Breaks, and Fragile Sites Chromosomal translocations are structural aberrations characterized by relocations of chromosomal segments within one or among different chromosomes. As chromosomal translocations are relatively stable structural changes 76-78 , they would be expected to accumulate with age. Several investigators have found that the increase in translocation frequencies in a nonsmoking normal population follows a curvilinear relationship with age 79,80 ....

Wrn Gene Product

Functional Domains of WRN Gene Product The WRN gene comprises 35 exons on the short arm of chromosome 8 and encodes protein of 1,432 amino acids. It was identified in 1996 using a conventional positional cloning approach 1 and the methods that were available at that time 16 . Simple alignment in database searches and more complicated structural studies showed four defined regions of WRNp. These include exonuclease domains I, II, and III in the N-terminal region 17,18 RecQ-type helicase...

Dna Repair And Telomeric Function

Telomerase-Deficient Mice with Short Telomeres Are Hypersensitive to Ionizing Radiation Double-strand breaks DSBs are generated by reactive by-products of oxygen metabolism, by exposure to ionizing radiation, and in V D J recombination in lymphocytes. Efficient DSB DNA repair machinery eliminates these breaks, which might otherwise cause increased death or tumorigenesis. There is increasing evidence that short telomeres result in increased organismal sensitivity to ionizing radiation. Short...