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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
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