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Nonspecific Binding of RNA to PARP1 and PARP2 Does Not Lead to Catalytic Activation
journal contribution
posted on 2019-12-15, 21:13 authored by Meagan
Y. Nakamoto, Johannes Rudolph, Deborah S. Wuttke, Karolin LugerPoly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2,
respectively),
upon binding damaged DNA, become activated to add long chains of poly(ADP-ribose)
(PAR) to themselves and other nuclear proteins. This activation is
an essential part of the DNA damage response. The PAR modifications
recruit the DNA repair machinery to sites of DNA damage and result
in base excision and single-strand break repair, homologous recombination,
nucleotide excision repair, and alternative nonhomologous end joining.
More recently, both PARP1 and PARP2 have been shown to bind to or
be activated by RNA, a property that could interfere with the function
of PARP1 and PARP2 in the response to DNA damage or lead to necrosis
by depletion of cellular NAD+. We have quantitatively evaluated
the in vitro binding of a variety of RNAs to PARP1 and PARP2 and queried
the ability of these RNAs to switch on enzymatic activity. We find
that while both proteins bind RNAs without specificity toward sequence
or structure, their interaction with RNA does not lead to auto-PARylation.
Thus, although PARP1 and PARP2 are promiscuous with respect to activation
by DNA, they both demonstrate exquisite selectivity against activation
by RNA.