Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(APLF). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Toronto

1. Tran, Diana. Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF.

Degree: 2012, University of Toronto

APLF (Aprataxin and Polynucleotide kinase/phosphatase-Like Factor) is an FHA (forkhead-associated)-domain-containing nuclear protein that facilitates the repair of single-strand and double-strand breaks (SSBs and DSBs). Specifically, the APLF-FHA domain mediates interactions with XRCC1 and XRCC4, factors involved in SSB and DSB repair, respectively. A novel substitution was identified in pancreatic cancer patients, where a conserved histidine was substituted to leucine (H42L) in the APLF-FHA domain. The functional and biological characterization of this “variant of unknown significance” was investigated. This thesis shows that the H42L substitution affects APLF phosphorylation, impairs APLF retention at laser-induced DNA breaks, disrupts protein-binding to XRCC1 but not to XRCC4, and reduces cell survival following irradiation and etoposide exposure. Collectively, these data suggest that the H42L substitution impacts APLF participation in global DNA damage repair. The findings from this work could provide insight into the role of APLF in genomic integrity and, moreover, in cancer predisposition.

MAST

Advisors/Committee Members: Koch, Christine Anne, Medical Biophysics.

Subjects/Keywords: APLF; FHA mutant; 0760; 0992; 0574

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tran, D. (2012). Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/33567

Chicago Manual of Style (16th Edition):

Tran, Diana. “Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF.” 2012. Masters Thesis, University of Toronto. Accessed August 19, 2019. http://hdl.handle.net/1807/33567.

MLA Handbook (7th Edition):

Tran, Diana. “Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF.” 2012. Web. 19 Aug 2019.

Vancouver:

Tran D. Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2019 Aug 19]. Available from: http://hdl.handle.net/1807/33567.

Council of Science Editors:

Tran D. Functional Characterization of a Novel Substitution in the Human DNA Repair Protein APLF. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/33567


University of Toronto

2. Shirodkar, Purnata V. Characterization of APLF in Non-homologous End-joining.

Degree: 2011, University of Toronto

APLF (Aprataxin and Polynucleotide kinase-Like Factor), a novel protein with a forkhead-associated (FHA) domain and two poly(ADP-ribose)-binding zinc fingers (PBZ), interacts with core non-homologous end-joining (NHEJ) repair factors, Ku and XRCC4-DNA ligase IV, and facilitates NHEJ. However, how APLF functions in NHEJ is undefined. This thesis demonstrates that the Ku-binding domain on APLF is mapped to amino acid residues 180-200, where conserved amino acid residue W189 strongly contributes to the APLF-Ku interaction. Remarkably, the APLF-Ku interaction is involved in the nuclear localization of APLF. Furthermore, we demonstrate that the N-terminal region (amino acids 1-200), containing the XRCC4-Ligase IV and Ku binding domains, is required for APLF- dependent NHEJ. Collectively, these findings suggest that Ku contributes to APLF nuclear localization, and that once APLF is retained in the nucleus, the N-terminal portion of APLF, which facilitates interactions with the core NHEJ proteins Ku and XRCC4-DNA ligase IV, is required for efficient NHEJ.

MAST

Advisors/Committee Members: Koch, Christine Anne, Medical Biophysics.

Subjects/Keywords: APLF; Non-homologous End-joining; Ku; nuclear localization; 0760; 0307

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Shirodkar, P. V. (2011). Characterization of APLF in Non-homologous End-joining. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/29632

Chicago Manual of Style (16th Edition):

Shirodkar, Purnata V. “Characterization of APLF in Non-homologous End-joining.” 2011. Masters Thesis, University of Toronto. Accessed August 19, 2019. http://hdl.handle.net/1807/29632.

MLA Handbook (7th Edition):

Shirodkar, Purnata V. “Characterization of APLF in Non-homologous End-joining.” 2011. Web. 19 Aug 2019.

Vancouver:

Shirodkar PV. Characterization of APLF in Non-homologous End-joining. [Internet] [Masters thesis]. University of Toronto; 2011. [cited 2019 Aug 19]. Available from: http://hdl.handle.net/1807/29632.

Council of Science Editors:

Shirodkar PV. Characterization of APLF in Non-homologous End-joining. [Masters Thesis]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/29632

.