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B21-High Throughput SAXS	Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription Ália Dos Santos , Daniel E. Rollins , Yukti Hari-Gupta , Hannah Mcarthur , Mingxue Du , Sabrina Yong Zi Ru , Kseniia Pidlisna , Ane Stranger , Faeeza Lorgat , Danielle Lambert , Ian Brown , Kevin Howland , Jesse Aaron , Lin Wang , Peter J. I. Ellis , Teng-Leong Chew , Marisa Martin-Fernandez , Alice L. B. Pyne , Christopher P. Toseland Nature Communications 14 DOI: 10.1038/s41467-023-38572-9 Diamond Proposal Number(s): [16207] Open Access Show Abstract ▼ Abstract: NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We find that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation.	May 2023

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B21-High Throughput SAXS

Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription