scholarly journals CRN13 candidate effectors from plant and animal eukaryotic pathogens are DNA-binding proteins which trigger host DNA damage response

2015 ◽  
Vol 210 (2) ◽  
pp. 602-617 ◽  
Author(s):  
Diana Ramirez-Garcés ◽  
Laurent Camborde ◽  
Michiel J. C. Pel ◽  
Alain Jauneau ◽  
Yves Martinez ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Damage Response ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Damage Response

scholarly journals PARprolink: a photoaffinity probe for identifying poly(ADP-ribose)-binding proteins

2020 ◽  
Author(s):  
Morgan Dasovich ◽  
Morgan Q. Beckett ◽  
Scott Bailey ◽  
Shao-En Ong ◽  
Marc M. Greenberg ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Rna Processing ◽  
Binding Proteins ◽  
Post Translational Modification ◽  
Mobility Shift ◽  
Binding Partners ◽  
Damage Response ◽  
Prostate Cancers ◽  
Electrophoretic Mobility Shift Assays

ABSTRACTPost-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently been approved for the treatment of breast, ovarian, and prostate cancers. Despite its clinical significance, a molecular understanding of PAR function, including its binding partners, remains incomplete. In this work, we synthesize a PAR photoaffinity probe that captures and isolates endogenous PAR binders. Our method identified dozens of known PAR-binding proteins and hundreds of novel binders involved in DNA repair, RNA processing, and metabolism. PAR binding by eight candidates was confirmed using pull-down and/or electrophoretic mobility shift assays. Using PAR probes of defined lengths, we detected proteins that preferentially bind to 40-mer over 8-mer PAR, indicating that polymer length may regulate the outcome and timing of PAR signaling pathways. This investigation produces the first census of PAR-binding proteins, provides a proteome-wide view of length-selective PAR binding, and associates PAR binding with RNA metabolism and the formation of biomolecular condensates.

scholarly journals The evolution of metazoan shelterin

2021 ◽  
Author(s):  
Logan R. Myler ◽  
Charles G. Kinzig ◽  
Nanda K. Sasi ◽  
George Zakusilo ◽  
Sarah W. Cai ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Dna Binding Proteins ◽  
Telomeric Dna ◽  
Evolutionary Origins ◽  
Variable Nature ◽  
Damage Response ◽  
Unicellular Organisms ◽  
Ob Fold ◽  
Regulate Telomere Length

The mammalian telomeric shelterin complex—comprised of TRF1, TRF2, Rap1, TIN2, TPP1, and POT1—blocks the DNA damage response at chromosome ends and interacts with telomerase and the CST complex to regulate telomere length. The evolutionary origins of shelterin are unclear, partly because unicellular organisms have distinct telomeric proteins. Here, we describe the evolution of metazoan shelterin, showing that TRF1 emerged in vertebrates upon duplication of a TRF2-like ancestor. TRF1 and TRF2 diverged rapidly during vertebrate evolution through the acquisition of new domains and interacting factors. Vertebrate shelterin is also distinguished by the presence of an HJRL domain in the split C-terminal OB fold of POT1, whereas invertebrate POT1s carry inserts of variable nature. Importantly, the data reveal that, apart from the primate and rodent POT1 orthologs, all metazoan POT1s are predicted to have a fourth OB fold at their N termini. Therefore, we propose that POT1 arose from a four-OB-fold ancestor, most likely an RPA70-like protein. This analysis provides insights into the biology of shelterin and its evolution from ancestral telomeric DNA-binding proteins.

scholarly journals Structure and DNA damage-dependent derepression mechanism for the XRE family member DG-DdrO

2019 ◽  
Vol 47 (18) ◽  
pp. 9925-9933 ◽  
Author(s):  
Huizhi Lu ◽  
Liangyan Wang ◽  
Shengjie Li ◽  
Chaoming Pan ◽  
Kaiying Cheng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Damage Response ◽  
Hydrophobic Interactions ◽  
Salt Bridge ◽  
Damage Response ◽  
Promoter Dna ◽  
Α Helix ◽  
Oppositely Charged ◽  
Insight Into

Abstract DdrO is an XRE family transcription repressor that, in coordination with the metalloprotease PprI, is critical in the DNA damage response of Deinococcus species. Here, we report the crystal structure of Deinococcus geothermalis DdrO. Biochemical and structural studies revealed the conserved recognizing α-helix and extended dimeric interaction of the DdrO protein, which are essential for promoter DNA binding. Two conserved oppositely charged residues in the HTH motif of XRE family proteins form salt bridge interactions that are essential for promoter DNA binding. Notably, the C-terminal domain is stabilized by hydrophobic interactions of leucine/isoleucine-rich helices, which is critical for DdrO dimerization. Our findings suggest that DdrO is a novel XRE family transcriptional regulator that forms a distinctive dimer. The structure also provides insight into the mechanism of DdrO-PprI-mediated DNA damage response in Deinococcus.

scholarly journals Functional Dissection of Human and Mouse POT1 Proteins

2008 ◽  
Vol 29 (2) ◽  
pp. 471-482 ◽  
Author(s):  
Wilhelm Palm ◽  
Dirk Hockemeyer ◽  
Tatsuya Kibe ◽  
Titia de Lange
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Damage Response ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Telomeric Dna ◽  
C Terminus ◽  
Damage Response ◽  
End Resection

ABSTRACT The single-stranded telomeric DNA binding protein POT1 protects mammalian chromosome ends from the ATR-dependent DNA damage response, regulates telomerase-mediated telomere extension, and limits 5′-end resection at telomere termini. Whereas most mammals have a single POT1 gene, mice have two POT1 proteins that are functionally distinct. POT1a represses the DNA damage response, and POT1b controls 5′-end resection. In contrast, as we report here, POT1a and POT1b do not differ in their ability to repress telomere recombination. By swapping domains, we show that the DNA binding domain of POT1a specifies its ability to repress the DNA damage response. However, no differences were detected in the in vitro DNA binding features of POT1a and POT1b. In contrast to the repression of ATR signaling by POT1a, the ability of POT1b to control 5′-end resection was found to require two regions in the C terminus, one corresponding to the TPP1 binding domain and a second representing a new domain located between amino acids (aa) 300 and 350. Interestingly, the DNA binding domain of human POT1 can replace that of POT1a to repress ATR signaling, and the POT1b region from aa 300 to 350 required for the regulation of the telomere terminus is functionally conserved in human POT1. Thus, human POT1 combines the features of POT1a and POT1b.

scholarly journals Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response

Cell Research ◽  
2013 ◽  
Vol 23 (10) ◽  
pp. 1215-1228 ◽  
Author(s):  
Yucai Wang ◽  
Xiao Han ◽  
Fangming Wu ◽  
Justin W Leung ◽  
Megan G Lowery ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Structure Analysis ◽  
Dna Damage Response ◽  
Binding Activity ◽  
Single Stranded Dna ◽  
Dna Binding Activity ◽  
Damage Response

scholarly journals FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response

2014 ◽  
Vol 42 (18) ◽  
pp. 11560-11569 ◽  
Author(s):  
Zhi-Wei Chen ◽  
Bin Liu ◽  
Nai-Wang Tang ◽  
Yun-Hua Xu ◽  
Xiang-Yun Ye ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Binding ◽  
Dna Damage Response ◽  
Binding Protein ◽  
Dna Binding Protein ◽  
Single Stranded Dna ◽  
Damage Response
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