DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair

DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2005-09, Vol.280 (36), p.31641-31647
Main Authors: Braithwaite, Elena K., Kedar, Padmini S., Lan, Li, Polosina, Yaroslava Y., Asagoshi, Kenjiro, Poltoratsky, Vladimir P., Horton, Julie K., Miller, Holly, Teebor, George W., Yasui, Akira, Wilson, Samuel H.
Format: Article
Language:English
Subjects:
Animals
Cell Line
DNA Damage - genetics
DNA Damage - physiology
DNA Glycosylases - metabolism
DNA Polymerase beta - deficiency
DNA Polymerase beta - genetics
DNA Polymerase beta - physiology
DNA Repair - genetics
DNA Repair - physiology
Fibroblasts - physiology
HeLa Cells
Humans
Mice
Oxidants - chemistry
Oxidation-Reduction
Pentoxyl - analogs & derivatives
Pentoxyl - pharmacology
Uracil-DNA Glycosidase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393
cites cdi_FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393
container_end_page 31647
container_issue 36
container_start_page 31641
container_title The Journal of biological chemistry
container_volume 280
creator Braithwaite, Elena K.
Kedar, Padmini S.
Lan, Li
Polosina, Yaroslava Y.
Asagoshi, Kenjiro
Poltoratsky, Vladimir P.
Horton, Julie K.
Miller, Holly
Teebor, George W.
Yasui, Akira
Wilson, Samuel H.
description DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.
doi_str_mv 10.1074/jbc.C500256200
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_17415069</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S002192582079280X</els_id><sourcerecordid>17415069</sourcerecordid><originalsourceid>FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393</originalsourceid><addsrcrecordid>eNp1kMlOwzAQhi0EoqVw5Yh84pbiJW6SY1VWiU0sEjfLy6RyldTFThE8G-_AM-GqlcqFuczon29-aX6EjikZUlLkZzNthhNBCBMjRsgO6lNS8owL-raL-kmmWcVE2UMHMc5Iqryi-6hHR2mVE9FHn-f3Y_zom68WgoqAf77xY_AdmC7iO79MyqXTwetGxaSoqXLz2OGHT2dV5z4Ar87PVaumgNXc4puIn8CEpevA4s7j5zRE7Os_3NkTLJQLh2ivVk2Eo00foNfLi5fJdXb7cHUzGd9mhhe8y8BUNWFcl9yOtKiLImdcMc0NE6uVsbQiggPnlmrNBGVlxUXFVV1rYJZXfIBO176L4N-XEDvZumigadQc0n-SFjkVZLQCh2vQBB9jgFougmtV-JKUyFXWMmUtt1mng5ON81K3YLf4JtwElGsA0n8fDoKMxsHcgHUhBSytd_95_wIjtoz_</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17415069</pqid></control><display><type>article</type><title>DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair</title><source>ScienceDirect</source><source>PMC (PubMed Central)</source><creator>Braithwaite, Elena K. ; Kedar, Padmini S. ; Lan, Li ; Polosina, Yaroslava Y. ; Asagoshi, Kenjiro ; Poltoratsky, Vladimir P. ; Horton, Julie K. ; Miller, Holly ; Teebor, George W. ; Yasui, Akira ; Wilson, Samuel H.</creator><creatorcontrib>Braithwaite, Elena K. ; Kedar, Padmini S. ; Lan, Li ; Polosina, Yaroslava Y. ; Asagoshi, Kenjiro ; Poltoratsky, Vladimir P. ; Horton, Julie K. ; Miller, Holly ; Teebor, George W. ; Yasui, Akira ; Wilson, Samuel H.</creatorcontrib><description>DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.C500256200</identifier><identifier>PMID: 16002405</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Line ; DNA Damage - genetics ; DNA Damage - physiology ; DNA Glycosylases - metabolism ; DNA Polymerase beta - deficiency ; DNA Polymerase beta - genetics ; DNA Polymerase beta - physiology ; DNA Repair - genetics ; DNA Repair - physiology ; Fibroblasts - physiology ; HeLa Cells ; Humans ; Mice ; Oxidants - chemistry ; Oxidation-Reduction ; Pentoxyl - analogs &amp; derivatives ; Pentoxyl - pharmacology ; Uracil-DNA Glycosidase</subject><ispartof>The Journal of biological chemistry, 2005-09, Vol.280 (36), p.31641-31647</ispartof><rights>2005 © 2005 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393</citedby><cites>FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S002192582079280X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3535,27903,27904,45759</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16002405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Braithwaite, Elena K.</creatorcontrib><creatorcontrib>Kedar, Padmini S.</creatorcontrib><creatorcontrib>Lan, Li</creatorcontrib><creatorcontrib>Polosina, Yaroslava Y.</creatorcontrib><creatorcontrib>Asagoshi, Kenjiro</creatorcontrib><creatorcontrib>Poltoratsky, Vladimir P.</creatorcontrib><creatorcontrib>Horton, Julie K.</creatorcontrib><creatorcontrib>Miller, Holly</creatorcontrib><creatorcontrib>Teebor, George W.</creatorcontrib><creatorcontrib>Yasui, Akira</creatorcontrib><creatorcontrib>Wilson, Samuel H.</creatorcontrib><title>DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.</description><subject>Animals</subject><subject>Cell Line</subject><subject>DNA Damage - genetics</subject><subject>DNA Damage - physiology</subject><subject>DNA Glycosylases - metabolism</subject><subject>DNA Polymerase beta - deficiency</subject><subject>DNA Polymerase beta - genetics</subject><subject>DNA Polymerase beta - physiology</subject><subject>DNA Repair - genetics</subject><subject>DNA Repair - physiology</subject><subject>Fibroblasts - physiology</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Mice</subject><subject>Oxidants - chemistry</subject><subject>Oxidation-Reduction</subject><subject>Pentoxyl - analogs &amp; derivatives</subject><subject>Pentoxyl - pharmacology</subject><subject>Uracil-DNA Glycosidase</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNp1kMlOwzAQhi0EoqVw5Yh84pbiJW6SY1VWiU0sEjfLy6RyldTFThE8G-_AM-GqlcqFuczon29-aX6EjikZUlLkZzNthhNBCBMjRsgO6lNS8owL-raL-kmmWcVE2UMHMc5Iqryi-6hHR2mVE9FHn-f3Y_zom68WgoqAf77xY_AdmC7iO79MyqXTwetGxaSoqXLz2OGHT2dV5z4Ar87PVaumgNXc4puIn8CEpevA4s7j5zRE7Os_3NkTLJQLh2ivVk2Eo00foNfLi5fJdXb7cHUzGd9mhhe8y8BUNWFcl9yOtKiLImdcMc0NE6uVsbQiggPnlmrNBGVlxUXFVV1rYJZXfIBO176L4N-XEDvZumigadQc0n-SFjkVZLQCh2vQBB9jgFougmtV-JKUyFXWMmUtt1mng5ON81K3YLf4JtwElGsA0n8fDoKMxsHcgHUhBSytd_95_wIjtoz_</recordid><startdate>20050909</startdate><enddate>20050909</enddate><creator>Braithwaite, Elena K.</creator><creator>Kedar, Padmini S.</creator><creator>Lan, Li</creator><creator>Polosina, Yaroslava Y.</creator><creator>Asagoshi, Kenjiro</creator><creator>Poltoratsky, Vladimir P.</creator><creator>Horton, Julie K.</creator><creator>Miller, Holly</creator><creator>Teebor, George W.</creator><creator>Yasui, Akira</creator><creator>Wilson, Samuel H.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope></search><sort><creationdate>20050909</creationdate><title>DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair</title><author>Braithwaite, Elena K. ; Kedar, Padmini S. ; Lan, Li ; Polosina, Yaroslava Y. ; Asagoshi, Kenjiro ; Poltoratsky, Vladimir P. ; Horton, Julie K. ; Miller, Holly ; Teebor, George W. ; Yasui, Akira ; Wilson, Samuel H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Cell Line</topic><topic>DNA Damage - genetics</topic><topic>DNA Damage - physiology</topic><topic>DNA Glycosylases - metabolism</topic><topic>DNA Polymerase beta - deficiency</topic><topic>DNA Polymerase beta - genetics</topic><topic>DNA Polymerase beta - physiology</topic><topic>DNA Repair - genetics</topic><topic>DNA Repair - physiology</topic><topic>Fibroblasts - physiology</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Mice</topic><topic>Oxidants - chemistry</topic><topic>Oxidation-Reduction</topic><topic>Pentoxyl - analogs &amp; derivatives</topic><topic>Pentoxyl - pharmacology</topic><topic>Uracil-DNA Glycosidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Braithwaite, Elena K.</creatorcontrib><creatorcontrib>Kedar, Padmini S.</creatorcontrib><creatorcontrib>Lan, Li</creatorcontrib><creatorcontrib>Polosina, Yaroslava Y.</creatorcontrib><creatorcontrib>Asagoshi, Kenjiro</creatorcontrib><creatorcontrib>Poltoratsky, Vladimir P.</creatorcontrib><creatorcontrib>Horton, Julie K.</creatorcontrib><creatorcontrib>Miller, Holly</creatorcontrib><creatorcontrib>Teebor, George W.</creatorcontrib><creatorcontrib>Yasui, Akira</creatorcontrib><creatorcontrib>Wilson, Samuel H.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Braithwaite, Elena K.</au><au>Kedar, Padmini S.</au><au>Lan, Li</au><au>Polosina, Yaroslava Y.</au><au>Asagoshi, Kenjiro</au><au>Poltoratsky, Vladimir P.</au><au>Horton, Julie K.</au><au>Miller, Holly</au><au>Teebor, George W.</au><au>Yasui, Akira</au><au>Wilson, Samuel H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2005-09-09</date><risdate>2005</risdate><volume>280</volume><issue>36</issue><spage>31641</spage><epage>31647</epage><pages>31641-31647</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>DNA polymerase λ (pol λ) is a member of the X family of DNA polymerases that has been implicated in both base excision repair and non-homologous end joining through in vitro studies. However, to date, no phenotype has been associated with cells deficient in this DNA polymerase. Here we show that pol λ null mouse fibroblasts are hypersensitive to oxidative DNA damaging agents, suggesting a role of pol λ in protection of cells against the cytotoxic effects of oxidized DNA. Additionally, pol λ co-immunoprecipitates with an oxidized base DNA glycosylase, single-strand-selective monofunctional uracil-DNA glycosylase (SMUG1), and localizes to oxidative DNA lesions in situ. From these data, we conclude that pol λ protects cells against oxidative stress and suggest that it participates in oxidative DNA damage base excision repair.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16002405</pmid><doi>10.1074/jbc.C500256200</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0021-9258
ispartof The Journal of biological chemistry, 2005-09, Vol.280 (36), p.31641-31647
issn 0021-9258
1083-351X
language eng
recordid cdi_proquest_miscellaneous_17415069
source ScienceDirect; PMC (PubMed Central)
subjects Animals
Cell Line
DNA Damage - genetics
DNA Damage - physiology
DNA Glycosylases - metabolism
DNA Polymerase beta - deficiency
DNA Polymerase beta - genetics
DNA Polymerase beta - physiology
DNA Repair - genetics
DNA Repair - physiology
Fibroblasts - physiology
HeLa Cells
Humans
Mice
Oxidants - chemistry
Oxidation-Reduction
Pentoxyl - analogs & derivatives
Pentoxyl - pharmacology
Uracil-DNA Glycosidase
title DNA Polymerase λ Protects Mouse Fibroblasts against Oxidative DNA Damage and Is Recruited to Sites of DNA Damage/Repair
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T02%3A45%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20Polymerase%20%CE%BB%20Protects%20Mouse%20Fibroblasts%20against%20Oxidative%20DNA%20Damage%20and%20Is%20Recruited%20to%20Sites%20of%20DNA%20Damage/Repair&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Braithwaite,%20Elena%20K.&rft.date=2005-09-09&rft.volume=280&rft.issue=36&rft.spage=31641&rft.epage=31647&rft.pages=31641-31647&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.C500256200&rft_dat=%3Cproquest_cross%3E17415069%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c373t-ec9f023b83d6b5f77423a2b3c25ec9fcd19053e33d1bb2512893593affbe2d393%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=17415069&rft_id=info:pmid/16002405&rfr_iscdi=true