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Biomedical subjects

Jörg Diefenbach

Publications and source records attributed to Jörg Diefenbach.

2 recordsLinked to original sources
PubMed2005

Ageing and PARP.

Poly(ADP-ribosyl)ation, which is the posttranslational modification of proteins with poly(ADP-ribose), is catalysed by poly(ADP-ribose) polymerases. DNA-strand break induced catalytic activation of two PARP isoforms, namely PARP-1 and -2, are in involved in DNA base-excision repair and other repair pathways. A body of correlative data suggests a link between DNA-damage induced poly(ADP-ribosyl)ation and mammalian longevity. This notion was reinforced by recently published evidence for interactions between PARP-1 and the Werner syndrome protein, deficiency of which causes premature ageing in humans. Recent research on PARPs and poly(ADP-ribose) provides several candidate mechanisms through which poly(ADP-ribosyl)ation might contribute to keeping the ageing process at slow pace.

Aging↗
PubMed2004

The emerging role of poly(ADP-ribose) polymerase-1 in longevity.

In the present paper, the involvement of the family of poly(ADP-ribose) polymerases (PARPs), and especially of PARP-1, in mammalian longevity is reviewed. PARPs catalyse poly(ADP-ribosyl)ation, a covalent post-translational protein modification in eukaryotic cells. PARP-1 and PARP-2 are activated by DNA strand breaks, play a role in DNA base-excision repair (BER) and are survival factors for cells exposed to low doses of ionising radiation or alkylating agents. PARP-1 is the main catalyst of poly(ADP-ribosyl)ation in living cells under conditions of DNA breakage, accounting for about 90% of cellular poly(ADP-ribose). DNA-damage-induced poly(ADP-ribosyl)ation also functions as a negative regulator of DNA damage-induced genomic instability. Cellular poly(ADP-ribosyl)ation capacity in permeabilised mononuclear blood cells (MNC) is positively correlated with life span of mammalian species. Furthermore PARP-1 physically interacts with WRN, the protein deficient in Werner syndrome, a human progeroid disorder, and PARP-1 and WRN functionally cooperate in preventing carcinogenesis in vivo. Some of the other members of the PARP family have also been revealed as important regulators of cellular functions relating to ageing/longevity. In particular, tankyrase-1, tankyrase-2, PARP-2 as well as PARP-1 have been found in association with telomeric DNA and are able to poly(ADP-ribosyl)ate the telomere-binding proteins TRF-1 and TRF-2, thus blocking their DNA-binding activity and controlling telomere extension by telomerase.

Animals↗