scholarly journals Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation

2012 ◽  
Vol 14 (4) ◽  
pp. 355-365 ◽  
Author(s):  
Marzia Fumagalli ◽  
Francesca Rossiello ◽  
Michela Clerici ◽  
Sara Barozzi ◽  
Davide Cittaro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Telomeric Dna ◽  
Damage Response ◽  
Response Activation

scholarly journals Erratum: Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation

2012 ◽  
Vol 14 (5) ◽  
pp. 555-555 ◽  
Author(s):  
Marzia Fumagalli ◽  
Francesca Rossiello ◽  
Michela Clerici ◽  
Sara Barozzi ◽  
Davide Cittaro ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Telomeric Dna ◽  
Damage Response ◽  
Response Activation

scholarly journals DNA Damage-Induced Phosphorylation of TRF2 Is Required for the Fast Pathway of DNA Double-Strand Break Repair

2009 ◽  
Vol 29 (13) ◽  
pp. 3597-3604 ◽  
Author(s):  
Nazmul Huda ◽  
Hiromi Tanaka ◽  
Marc S. Mendonca ◽  
David Gilley
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Functional Role ◽  
Strand Break ◽  
Telomere Maintenance ◽  
Telomeric Dna ◽  
Dsb Repair ◽  
Dna Double Strand Break ◽  
Damage Response ◽  
Fast Pathway

ABSTRACT Protein kinases of the phosphatidylinositol 3-kinase-like kinase family, originally known to act in maintaining genomic integrity via DNA repair pathways, have been shown to also function in telomere maintenance. Here we focus on the functional role of DNA damage-induced phosphorylation of the essential mammalian telomeric DNA binding protein TRF2, which coordinates the assembly of the proteinaceous cap to disguise the chromosome end from being recognized as a double-stand break (DSB). Previous results suggested a link between the transient induction of human TRF2 phosphorylation at threonine 188 (T188) by the ataxia telangiectasia mutated protein kinase (ATM) and the DNA damage response. Here, we report evidence that X-ray-induced phosphorylation of TRF2 at T188 plays a role in the fast pathway of DNA DSB repair. These results connect the highly transient induction of human TRF2 phosphorylation to the DNA damage response machinery. Thus, we find that a protein known to function in telomere maintenance, TRF2, also plays a functional role in DNA DSB repair.

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 Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

2014 ◽  
Vol 21 (6) ◽  
pp. 998-1012 ◽  
Author(s):  
M Ogrunc ◽  
R Di Micco ◽  
M Liontos ◽  
L Bombardelli ◽  
M Mione ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Damage Response ◽  
Response Activation

Hepatitis B virus induces RNR-R2 expression via DNA damage response activation

2015 ◽  
Vol 63 (4) ◽  
pp. 789-796 ◽  
Author(s):  
Inna Ricardo-Lax ◽  
Vyas Ramanan ◽  
Eleftherios Michailidis ◽  
Tal Shamia ◽  
Nina Reuven ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Damage Response ◽  
B Virus ◽  
Damage Response ◽  
Response Activation
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