Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-5
pubmed:abstractText
Tyrosyl DNA phosphodiesterase (TDP1) is a DNA 3'-end processing enzyme that preferentially hydrolyses the bond between the 3'-end of DNA and stalled DNA topoisomerase 1. the importance of TDP1 is highlighted by its association with the human genetic disease spinocerebellar ataxia with axonal neuropathy. TDP1 comprises of a highly conserved C-terminus phosphodiesterase domain and a less conserved N-terminus tail. the importance of the N-terminus domain was suggested by its interaction with Lig3alpha. Here we show that this interaction is promoted by serine 81 that is located within a putative S/TQ site in the N-terminus domain of TDP1. Although mutation of serine 81 to alanine had no impact on TDP1 activity in vitro and had little impact on the ability of TDP1 to mediate the rapid repair of CPT- or IR-induced DNA breaks in vivo, it led to marked reduction of protein stability. Moreover, it reduced the ability of TDP1 to promote cell survival following genotoxic stress. Together, our findings highlight a novel mechanism for regulating TDP1 function in mammalian cells that is not directly related to its enzymatic activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
588-595
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage.
pubmed:affiliation
Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't