DICER, DROSHA and DNA damage response RNAs are necessary for the secondary recruitment of DNA damage response factors.

Journal of Cell Science
Sofia FranciaFabrizio d'Adda di Fagagna

Abstract

The DNA damage response (DDR) plays a central role in preserving genome integrity. Recently, we reported that the endoribonucleases DICER and DROSHA contribute to DDR activation by generating small non-coding RNAs, termed DNA damage response RNA (DDRNA), carrying the sequence of the damaged locus. It is presently unclear whether DDRNAs act by promoting the primary recognition of DNA lesions or the secondary recruitment of DDR factors into cytologically detectable foci and consequent signal amplification. Here, we demonstrate that DICER and DROSHA are dispensable for primary recruitment of the DDR sensor NBS1 to DNA damage sites. Instead, the accumulation of the DDR mediators MDC1 and 53BP1 (also known as TP53BP1), markers of secondary recruitment, is reduced in DICER- or DROSHA-inactivated cells. In addition, NBS1 (also known as NBN) primary recruitment is resistant to RNA degradation, consistent with the notion that RNA is dispensable for primary recognition of DNA lesions. We propose that DICER, DROSHA and DDRNAs act in the response to DNA damage after primary recognition of DNA lesions and, together with γH2AX, are essential for enabling the secondary recruitment of DDR factors and fuel the amplification of DDR signaling.

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Citations

Nov 9, 2016·Journal of Molecular Biology·Giuseppina D'Alessandro, Fabrizio d'Adda di Fagagna
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Methods Mentioned

BETA
FACS
electrophoresis
PCR
transfection
Fluorescence

Software Mentioned

FACSDiva
GraphPad Prism
MetaMorph
ImageJ
Leica LAS AF
ModFit LT
Leica Confocal
CellProfiler

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