Publications by authors named "Chatrin Chatrin"

Article Synopsis
  • Ubiquitination is the process of attaching ubiquitin to proteins, but recent studies show that certain E3 ligases, like DELTEX, can modify non-protein substrates, including ADP-ribose.* -
  • The DELTEX family member DTX3L specifically adds ubiquitin to single-stranded and double-stranded DNA/RNA, requiring its C-terminal RING and DTC domains for this catalytic activity.* -
  • This research highlights the novel role of DTX3L in ubiquitinating nucleic acids, paving the way for future exploration of the functional significance of this modification.*
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The recent discovery of non-proteinaceous ubiquitylation substrates broadened our understanding of this modification beyond conventional protein targets. However, the existence of additional types of substrates remains elusive. Here, we present evidence that nucleic acids can also be directly ubiquitylated via ester bond formation.

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PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation.

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Although ubiquitylation had traditionally been considered limited to proteins, the discovery of non-proteinaceous substrates (e.g. lipopolysaccharides and adenosine diphosphate ribose (ADPr)) challenged this perspective.

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PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates.

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Article Synopsis
  • AlphaFold2 and other computational tools have advanced structural biology by accurately predicting protein structures, particularly those of the human PARP protein family.
  • The study presents a comprehensive analysis of PARP proteins, detailing their structured domains, disordered regions, and functional roles related to protein and nucleic acid modification.
  • Key findings include a model for PARP1's dynamics in different states and confirmation of PARP14's capability to bind RNA and perform RNA ADP-ribosylation, although further experimental validation is necessary.
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Cellular cross-talk between ubiquitination and other posttranslational modifications contributes to the regulation of numerous processes. One example is ADP-ribosylation of the carboxyl terminus of ubiquitin by the E3 DTX3L/ADP-ribosyltransferase PARP9 heterodimer, but the mechanism remains elusive. Here, we show that independently of PARP9, the conserved carboxyl-terminal RING and DTC (Deltex carboxyl-terminal) domains of DTX3L and other human Deltex proteins (DTX1 to DTX4) catalyze ADP-ribosylation of ubiquitin's Gly Structural studies reveal a hitherto unknown function of the DTC domain in binding NAD Deltex RING domain recruits E2 thioesterified with ubiquitin and juxtaposes it with NAD bound to the DTC domain to facilitate ADP-ribosylation of ubiquitin.

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Cross-talk between ubiquitination and ADP-ribosylation regulates spatiotemporal recruitment of key players in many signaling pathways. The DELTEX family ubiquitin ligases (DTX1 to DTX4 and DTX3L) are characterized by a RING domain followed by a C-terminal domain (DTC) of hitherto unknown function. Here, we use two label-free mass spectrometry techniques to investigate the interactome and ubiquitinated substrates of human DTX2 and identify a large proportion of proteins associated with the DNA damage repair pathway.

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Zika virus, a flavivirus like Dengue and West Nile viruses, poses a significant risk as a pathogen in the category of emerging infectious diseases. Zika infections typically cause nonspecific, mild symptoms, but can also manifest as a neurological disorder like Guillain-Barré syndrome. Infection in pregnant women is linked to microcephaly in newborn infants.

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