Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation

Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation

Bibliographic Details
Main Author: Martinez, Alaina R.
Language:English
Published: The Ohio State University / OhioLINK 2016
Subjects:
Biomedical Research
Alternative lengthening of telomeres
C-circles
DNA mismatch repair
DNA repair
Homologous recombination
Telomere maintenance
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1479924417740462
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu14799244177404622021-08-03T06:39:09Z Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation Martinez, Alaina R. Biomedical Research Alternative lengthening of telomeres C-circles DNA mismatch repair DNA repair Homologous recombination Telomere maintenance The human genome relies on DNA repair proteins and the telomere to maintain genome stability. Genome instability is recognized as a hallmark of cancer, as is limitless replicative capacity. Cancer cells require telomere maintenance to enable this uncontrolled growth. Most often telomerase is activated, although a subset of human cancers depend on recombination-based mechanisms known as Alternative Lengthening of Telomeres (ALT). ALT depends invariably on recombination and its associated DNA repair proteins to extend telomeres. This study tested the hypothesis that the requirement for those requisite recombination proteins include other types of DNA repair proteins. These functions were tested in ALT cell lines using C-circle abundance as a marker of ALT. The requirement for homologous recombination proteins and other DNA repair proteins varied between ALT cell lines compared. Several proteins essential for homologous recombination were dispensable for C-circle production in some ALT cell lines, while proteins grouped into excision DNA repair processes were required for C-circle production. The MSH2 mismatch repair protein was required for telomere recombination by intertelomeric exchange. In sum, our study suggests that ALT proceeds by multiple mechanisms that differ between human cancer cell lines and that some of these depend on DNA repair proteins not associated with homologous recombination pathways. Further studies of all DNA repair pathways in ALT will likely lead to a better understanding of ALT mechanisms and ultimately better ALT-targeted therapeutics. 2016 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1479924417740462 http://rave.ohiolink.edu/etdc/view?acc_num=osu1479924417740462 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
Alternative lengthening of telomeres
C-circles
DNA mismatch repair
DNA repair
Homologous recombination
Telomere maintenance
spellingShingle Biomedical Research
Alternative lengthening of telomeres
C-circles
DNA mismatch repair
DNA repair
Homologous recombination
Telomere maintenance
Martinez, Alaina R.
Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
author Martinez, Alaina R.
author_facet Martinez, Alaina R.
author_sort Martinez, Alaina R.
title Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
title_short Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
title_full Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
title_fullStr Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
title_full_unstemmed Variant requirements for DNA repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
title_sort variant requirements for dna repair proteins in cancer cell lines that use alternative lengthening of telomere mechanisms of elongation
publisher The Ohio State University / OhioLINK
publishDate 2016
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1479924417740462
work_keys_str_mv AT martinezalainar variantrequirementsfordnarepairproteinsincancercelllinesthatusealternativelengtheningoftelomeremechanismsofelongation
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