Age to survive: DNA damage and aging

Schumacher, Björn; Garinis, George A.; Hoeijmakers, Jan H.J.

doi:10.1016/j.tig.2007.11.004

Cited by 222 publications

(191 citation statements)

References 85 publications

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“…CS and TTD patients are characterized by postnatal growth failure, skeletal and neuronal abnormalities, s.c. fat loss and short lifespan (collectively designated as "segmental" NER progeroid features), but not cancer (8). Mouse mutants with inborn NER defects closely mimic their human counterparts and display severe developmental abnormalities and short lifespan (9).…”

mentioning

confidence: 99%

Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria

Kamileri

Karakasilioti

Sideri

et al. 2012

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

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Nucleotide excision repair (NER) defects are associated with cancer, developmental disorders and neurodegeneration. However, with the exception of cancer, the links between defects in NER and developmental abnormalities are not well understood. Here, we show that the ERCC1-XPF NER endonuclease assembles on active promoters in vivo and facilitates chromatin modifications for transcription during mammalian development. We find that Ercc1 −/− mice demonstrate striking physiological, metabolic and gene expression parallels with Taf10 −/− animals carrying a liver-specific transcription factor II D (TFIID) defect in transcription initiation. Promoter occupancy studies combined with expression profiling in the liver and in vitro differentiation cell assays reveal that ERCC1-XPF interacts with TFIID and assembles with POL II and the basal transcription machinery on promoters in vivo. Whereas ERCC1-XPF is required for the initial activation of genes associated with growth, it is dispensable for ongoing transcription. Recruitment of ERCC1-XPF on promoters is accompanied by promoter-proximal DNA demethylation and histone marks associated with active hepatic transcription. Collectively, the data unveil a role of ERCC1/XPF endonuclease in transcription initiation establishing its causal contribution to NER developmental disorders.DNA damage | genetics | metabolism

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mentioning

confidence: 99%

Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria

Kamileri

Karakasilioti

Sideri

et al. 2012

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

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“…Much of the variation in patterns of mortality in nature may reflect variation in the ability of organisms to respond to naturally occurring stresses (Hughes and Reynolds, 2005;Parsons, 2007;Vleck et al, 2007;Kuningas et al, 2008;Mangel, 2008) and gene-mediating stress responses, either by avoiding or repairing damage, have been shown to have large effects on lifespan (Schumacher et al, 2008). We have no measures of oxidative or other physiological stressors (Conti, 2008), and how they vary with temperature, in C. maculatus.…”

Section: Discussionmentioning

confidence: 99%

Environmental effects on sex differences in the genetic load for adult lifespan in a seed-feeding beetle

Fox

Stillwell

2009

Heredity

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We have little understanding of how environmental conditions affect the expression of the genetic load for lifespan and adult mortality rates, or how this environmental dependence affect tests of models for the evolution of senescence. We use the seed-feeding beetle, Callosobruchus maculatus, as a model to explore how the inbreeding load (L) affecting adult lifespan varies with rearing conditions (diet and temperature), and how rearing conditions affect tests of the mutation accumulation model of senescence. When reared under benign conditions, there was a large sex difference in inbreeding depression (d) and the inbreeding load (L ¼ 0.51-0.86 lethal equivalents per gamete for females L ¼ B0 for males). This sex difference in L was dependent on temperature, but not on rearing host or heat shock. At both high and low temperatures (relative to intermediate temperature) L increased for males, and L converged for the sexes at low temperature (L ¼ 0.26-0.53 for both sexes). Correlations were small for L between pairs of temperatures, indicating that the genes responsible for the inbreeding load differed between temperatures. In contrast to predictions of the mutation accumulation model of senescence, the agespecific inbreeding load for the adult mortality rate (L u(t) ) did not increase with age in any rearing environment. The genetic load underlying lifespan and adult mortality rates, and large sex differences in the genetic load, is highly dependent on environmental conditions. Estimating the genetic load in benign laboratory environments may be insufficient to predict the genetics underlying lifespan variation in nature where environmental variation is the norm.

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“…In contrast, TC-NER is primarily responsible for protecting against a cytotoxic response to DNA damage (Mitchell et al, 2003;Schumacher et al, 2008). In the absence of TC-NER, UV induces erythema and edema (acute sunburn), but not skin cancer.…”

Section: Nucleotide Excision Repairmentioning

confidence: 99%

“…In contrast, mouse models of CS and TTD, with accelerated aging of multiple tissues, do not have an elevated spontaneous mutation frequency or an increased incidence of spontaneous internal tumors (Dolle et al, 2006). Thus mutations, arising from an NER defect, correlate with cancer but not aging, providing experimental evidence that mutations are not the driving force in aging (Mitchell et al, 2003;Schumacher et al, 2008) …”

Section: Cancermentioning

confidence: 99%

Tissue-specific accelerated aging in nucleotide excision repair deficiency

Niedernhofer

2008

Mechanisms of Ageing and Development

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Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helixdistorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple agerelated diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage.

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Age to survive: DNA damage and aging

Cited by 222 publications

References 85 publications

Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria

Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria

Environmental effects on sex differences in the genetic load for adult lifespan in a seed-feeding beetle

Tissue-specific accelerated aging in nucleotide excision repair deficiency

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