PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2).
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27530147.
- Also identified by DOI 10.1038/ncomms12404 and PMC identifier 4992063.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
PARP3 is a member of the ADP-ribosyl transferase superfamily that we show accelerates the repair of chromosomal DNA single-strand breaks in avian DT40 cells. Two-dimensional nuclear magnetic resonance experiments reveal that PARP3 employs a conserved DNA-binding interface to detect and stably bind DNA breaks and to accumulate at sites of chromosome damage. PARP3 preferentially binds to and is activated by mononucleosomes containing nicked DNA and which target PARP3 trans-ribosylation activity to a single-histone substrate. Although nicks in naked DNA stimulate PARP3 autoribosylation, nicks in mononucleosomes promote the trans-ribosylation of histone H2B specifically at Glu2. These data identify PARP3 as a molecular sensor of nicked nucleosomes and demonstrate, for the first time, the ribosylation of chromatin at a site-specific DNA single-strand break.
Medical subject headings
- DNA Breaks, Single-Stranded
- Histones
- Nucleosomes
- Poly(ADP-ribose) Polymerases
- Ribose