Novel insights NuRD in Cell Reports.

Spruijt, Nellke.jpg

Nelleke spruijt, theme Cancer development and Immune defense, together with collaborators from the Leiden University Medical Center published novel insights into the composition and function of the evolutionary conserved protein complex NuRD in Cell Reports.

The NuRD protein complex plays an important role in gene regulation and DNA damage repair. Dysregulation of either process may lead to diseases, such as cancer. This is why it is important to understand the function of the NuRD complex. Here, we show that the  ZMYND8 protein bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and only slightly affects expression of ZMYND8/NuRD target genes. In contrast, the MYND domain in ZMYND8 facilitates the rapid, poly(ADP-ribose)-dependent-recruitment of GATAD2A/NuRD to sites of DNA damage to promote repair by homologous recombination. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to distinct NuRD subcomplexes.

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