{"id":7290,"date":"2017-08-02T10:01:47","date_gmt":"2017-08-02T14:01:47","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?p=7290"},"modified":"2017-08-02T10:01:47","modified_gmt":"2017-08-02T14:01:47","slug":"dna-polymerase-theta-and-its-potential-role-in-cancer","status":"publish","type":"post","link":"https:\/\/web.uri.edu\/riinbre\/dna-polymerase-theta-and-its-potential-role-in-cancer\/","title":{"rendered":"DNA Polymerase Theta and its Potential Role in Cancer"},"content":{"rendered":"<p><strong>Investigator:<\/strong>\u00a0Jamie Towle-Weicksel, Rhode Island College<\/p>\n<p><strong>Mentor:\u00a0<\/strong>Sarah Delaney, Brown University<\/p>\n<p><strong>Scientific Theme:<\/strong>\u00a0Cancer<\/p>\n<p><strong>Abstract:<\/strong>\u00a0DNA is randomly damaged on a daily basis by many factors including environmental exposure and random replicative errors.\u00a0 This damaged DNA can lead to genomic instability and eventually cancer. The cell copes with this damage through DNA repair pathways and this proposed study focuses on one key member, DNA polymerase Theta (Pol \u03b8) or POLQ.\u00a0 DNA polymerases synthesize new DNA by \u201creading\u201d the original DNA template.\u00a0 Poorly functioning DNA polymerases have been shown to contribute to genetic instability by incorporating the wrong nucleic acid across from the original DNA template.\u00a0 Pol \u03b8 performs low fidelity repair for certain types of DNA damage.\u00a0 Interestingly, POLQ expression has been shown to be upregulated in several types of cancer and is associated with poor survival rates.\u00a0 There are limited research studies exploring aberrant Pol \u03b8 mutants and their link to cancer.\u00a0 We have identified several POLQ mutations from patient-derived melanomas and aim to study how their polymerization mechanisms differ from wild-type and how they may be a driver of cancer.\u00a0 Our preliminary studies suggest Pol \u03b8 variants experience different polymerase activity compared to wild-type Pol \u03b8 and we will continue to define the polymerase activity of these mutants.\u00a0 In addition, we will generate a fluorescence resonance energy transfer (FRET) system to track conformational changes that occur during nucleotide incorporation.\u00a0 This will provide a method in which to observe the pathway for nucleotide incorporation.\u00a0 By setting up such a system, we can compare movements of wild-type Pol \u03b8 compared to the cancer-associated variants to provide evidence for different kinetic pathways.\u00a0\u00a0 We hypothesize that variant Pol \u03b8 will exhibit a preference for incorporation of the incorrect nucleotide leading to mutagenesis of the DNA and experience different conformational changes during nucleotide incorporation compared to wild-type.\u00a0 This research is significant in that we aim to demonstrate a mechanism of carcinogenesis as well as identify a potential biomarker of melanoma.<\/p>\n<p><strong>Human Health Relevance:<\/strong>\u00a0DNA polymerases are necessary for maintaining DNA fildelity as increased mutagenesis has been associated with cancer.\u00a0 Pol \u03b8 may play an important role in overall genomic stability due to its DNA repair capabilities. By identifying and characterizing cancer-associated variants of Pol \u03b8 that have reduced DNA repair abilities, our studies will provide fundamental insight as to the mechanism of mutagenesis and cancer.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator:\u00a0Jamie Towle-Weicksel, Rhode Island College Mentor:\u00a0Sarah Delaney, Brown University Scientific Theme:\u00a0Cancer Abstract:\u00a0DNA is randomly damaged on a daily basis by many factors including environmental exposure and random replicative errors.\u00a0 This damaged DNA can lead to genomic instability and eventually cancer. The cell copes with this damage through DNA repair pathways and this proposed study focuses [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[96],"tags":[],"class_list":["post-7290","post","type-post","status-publish","format-standard","hentry","category-research"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts\/7290","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=7290"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/posts\/7290\/revisions"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=7290"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/categories?post=7290"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/tags?post=7290"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}