{"id":6291,"date":"2016-09-14T13:43:06","date_gmt":"2016-09-14T17:43:06","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=6291"},"modified":"2016-09-14T13:43:06","modified_gmt":"2016-09-14T17:43:06","slug":"dna-polmerase-theta-and-its-potential-role-in-cancer","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/surf-training-award\/dna-polmerase-theta-and-its-potential-role-in-cancer\/","title":{"rendered":"DNA polmerase theta and its potential role in cancer"},"content":{"rendered":"<p><strong>Investigator:<\/strong> Jamie Towle-Weicksel<\/p>\n<p><strong>Scientific Theme:<\/strong> Cancer<\/p>\n<p><strong>Abstract:<\/strong>\u00a0Cancer is a devastating disease that results from the uncontrollable growth of certain cells in the body and is\u00a0one of the leading causes of death in the United States. DNA is randomly damaged on daily basis by many\u00a0factors including environmental exposure, random error, or genetic inheritance. This damaged DNA can\u00a0lead to genomic instability and eventually cancer. Depending on the damage, the cell handles the stress in\u00a0different ways. Double stranded breaks are resolved by three potential end-joining pathways: homologous\u00a0recombination (HR); canonical non-homologous end joining (cNHEJ); or microhomology-mediated end\u00a0joining (MMEJ). HR typically occurs in S and G2 phases of the cell cycle and requires a sister chromosome\u00a0to provide a template for DNA synthesis. NHEJ occurs throughout the cell cycle, but results in loss of\u00a0nucleotides at the site of the break. An alternative pathway, that is also active throughout the cell cycle, is\u00a0MMEJ. The ends of the double-stranded DNA are resected exposing single-stranded DNA on either ends of\u00a0the break. Any homology within the DNA ends are aligned by the enzyme DNA polymerase \u03b8, which is thenable to fill in nucleotides at the gaps in the DNA. XRCC1-Ligase III \u03b1 seals the remaining nick in the DNA.This results in little loss in genetic information, but can be mutagenic.\u00a0This proposed study focuses on the A-family DNA polymerase theta (Pol \u03b8 or POLQ). It is a DNA repair\u00a0enzyme that is able to perform single base, template directed, low fidelity repair (Arana et al., 2008; Maga et\u00a0al., 2002; Prasad et al., 2009). POLQ gene expression has been shown to be upregulated in breast and\u00a0colorectal cancer (Lem\u00e9e et al., 2010; Pillaire et al., 2009). We have also identified Pol \u03b8 mutations from\u00a0patient derived melanomas in collaboration with the Tissue Resource Core of the Yale SPORE in Skin\u00a0Cancer. We hypothesize that aberrant Pol \u03b8 may be aid cancer cells during its growing stages. This study\u00a0would provide a mechanism of mutagenesis by understanding 1) how cancer-associated variants have\u00a0impaired fidelity and might contribute to carcinogenesis and 2) how the dynamics of the Pol \u03b8 is involved in\u00a0nucleotide selection and overall fidelity.<\/p>\n<p><strong>Human Health Relevance:\u00a0<\/strong>DNA polymerases are necessary for maintaining DNA fildelity as increased mutagenesis has been\u00a0associated with cancer. Pol \u03b8 may play an important role in overall genomic stability due to its DNA repair\u00a0capabilities. By identifying and characterizing cancer-associated variants of Pol \u03b8 that have reduced DNA\u00a0repair abilities, our studies will provide fundamental insight as to the mechanism of mutagenesis and cancer.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator: Jamie Towle-Weicksel Scientific Theme: Cancer Abstract:\u00a0Cancer is a devastating disease that results from the uncontrollable growth of certain cells in the body and is\u00a0one of the leading causes of death in the United States. DNA is randomly damaged on daily basis by many\u00a0factors including environmental exposure, random error, or genetic inheritance. This damaged DNA [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":10206,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-6291","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/6291","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=6291"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/6291\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/10206"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=6291"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}