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Universität zu Köln |
Björn Schumacher, Ph.D.
DNA Damage and Aging
We are investigating the molecular
mechanism of aging. Aging is strongly correlated with a host of human
pathologies, most prominently cancer and neurodegenerative diseases such
as Alzheimer’s and Parkinson’s, as
well as general functional decline. It is, therefore, of outstanding interest
to further our understanding of the mechanisms underlying human aging. DNA
damage has been shown to play a central role both in cancer and, more
recently, in premature aging. The causal role of DNA damage in cancer and
aging is particularly apparent in human patients that have inborn
deficiencies in nucleotide excision repair (NER). There are two distinct
branches of initial damage recognition; global genome (GG) NER scans the
entire genome for helix-distorting DNA lesions, whereas transcription-coupled
repair (TCR) detects lesions in actively transcribed genes. Strikingly,
GG-NER defects leads to skin cancer prone Xeroderma
pigmentosum (XP) whereas defective TCR gives rise to premature aging
(progeroid) syndromes Cockayne
syndrome (CS) and trichothiodystrophy (TTD. To
unravel the molecular mechanism through which DNA damage contributes to aging
we are using the genetic model organism Caenorhabditis elegans as well as mammalian disease models.
Excision repair in cancer and aging. UV lesions and helix-distorting
chemical adducts are recognized and repaired by a multi-protein nucleotide
excision repair (NER) complex comprising two pathways: global genome (GG) NER
and transcription-coupled excision repair (TCR). Patients who have a
defective GG-NER pathway are highly susceptible to skin cancer, whereas
defects in TCR lead to progeroid syndromes. Reproduced from
Schumacher, Bioessays 2009 |
