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

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.

Download Full-text

580. Insight into the Mechanism of Increased Transduction of AAV Vectors with Ad Proteins E1B55k/E4orf6 and Generalization to Other Substrates of the Cellular DNA Damage Response Pathway

Molecular Therapy ◽

10.1016/s1525-0016(16)36384-5 ◽

2012 ◽

Vol 20 ◽

pp. S225

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Damage Response ◽

Cellular Dna ◽

Dna Damage Response Pathway ◽

Insight Into

Download Full-text

An insight into the mechanism of DNA damage response in plants- role of SUPPRESSOR OF GAMMA RESPONSE 1: An overview

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ◽

10.1016/j.mrfmmm.2020.111689 ◽

2020 ◽

Vol 819-820 ◽

pp. 111689 ◽

Cited By ~ 2

Author(s):

Kalyan Mahapatra ◽

Sujit Roy

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Damage Response ◽

Insight Into

Download Full-text

DNA damage response induces structural alterations in histone H3–H4

Journal of Radiation Research ◽

10.1093/jrr/rrw086 ◽

2017 ◽

Vol 58 (1) ◽

pp. 59-65 ◽

Cited By ~ 7

Author(s):

Yudai Izumi ◽

Kentaro Fujii ◽

Satoshi Yamamoto ◽

Koichi Matsuo ◽

Hirofumi Namatame ◽

...

Keyword(s):

Dna Damage ◽

Chromatin Remodeling ◽

Dna Damage Response ◽

Histone H3 ◽

Structural Alteration ◽

Histone H2a ◽

Structural Alterations ◽

X Ray ◽

Damage Response ◽

Α Helix

Abstract Synchrotron-radiation circular-dichroism spectroscopy was used to reveal that the DNA damage response induces a decrement of α-helix and an increment of β-strand contents of histone H3–H4 extracted from X-ray–irradiated human HeLa cells. The trend of the structural alteration was qualitatively opposite to that of our previously reported results for histone H2A–H2B. These results strongly suggest that histones share roles in DNA damage responses, particularly in DNA repair processes and chromatin remodeling, via a specific structural alteration of each histone.

Download Full-text

Functional Dissection of Human and Mouse POT1 Proteins

Molecular and Cellular Biology ◽

10.1128/mcb.01352-08 ◽

2008 ◽

Vol 29 (2) ◽

pp. 471-482 ◽

Cited By ~ 69

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.

Download Full-text