Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487930
Title: The role of a divergent FHA domain in DNA single-strand break repair
Author: Iles, Natasha J.
ISNI:       0000 0001 3609 8474
Awarding Body: University of Sussex
Current Institution: University of Sussex
Date of Award: 2007
Availability of Full Text:
Access from EThOS:
Abstract:
XRCC1 plays a major role in the repair of these lesions in mammalian cells by binding and/or activating many components of the single-strand break repair (SSBR) pathway. One such component is polynucleotide kinase (PNK) which possesses a divergent forkhead associated (FHA) domain that binds CK2-phosphorylated XRCC1. Aprataxin has a similar divergent FHA domain that also interacts with XRCC1 and which has been implicated in SSBR. In this thesis, yeast two-hybrid analysis indicated that PNK interacted with the pro-apoptotic protein Hippi in a manner dependent on the PNK FHA domain. In addition, a novel protein containing a similar FHA domain to PNK and aprataxin was identified and denoted APLF (Aprataxin and PNK-Like Factor). APLF was also shown to bind XRCC1 in a manner dependent on its FHA domain. Furthermore, this interaction was greatly stimulated by CK2-phosphorylation of XRCC1. APLF interacted with the double-strand break repair (DSBR) factor XRCC4. APLF was modified following DNA damage, presumably by phosphorylation. Nuclear localisation of YFP-APLF was promoted by the presence of XRCC1. Moreover, YFP-APLF colocalised with RFP-XRCC1 in DNA damage-induced nuclear foci following H₂O₂ treatment. Novel interaction partners of APLF identified by employing a yeast two-hybrid library screen included Ku86/XRCC5 and KEAP1. These data suggest a role for APLF in the cellular response to DNA strand breaks.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.487930  DOI: Not available
Share: