Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F12%3A00390248" target="_blank" >RIV/68378050:_____/12:00390248 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1093/nar/gks648" target="_blank" >http://dx.doi.org/10.1093/nar/gks648</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gks648" target="_blank" >10.1093/nar/gks648</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage

Popis výsledku v původním jazyce

Reactive oxygen species constantly generated as by-products of cellular metabolism readily attack genomic DNA creating mutagenic lesions such as 7,8-dihydro-8-oxo-guanine (8-oxo-G) that promote aging. 8-oxo-G:A mispairs arising during DNA replication areeliminated by base excision repair initiated by the MutY DNA glycosylase homologue (MUTYH). Here, by using formaldehyde crosslinking in mammalian cell extracts, we demonstrate that the WRN helicase/exonuclease defective in the premature aging disorder Werner syndrome (WS) is recruited to DNA duplex containing an 8-oxo-G:A mispair in a manner dependent on DNA polymerase lambda (Pol lambda) that catalyzes accurate DNA synthesis over 8-oxo-G. Similarly, by immunofluorescence, we show that Pol lambda is required for accumulation of WRN at sites of 8-oxo-G lesions in human cells. Moreover, we show that nuclear focus formation of WRN and Pol lambda induced by oxidative stress is dependent on ongoing DNA replication and on the presence of MUT

Název v anglickém jazyce

Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage

Popis výsledku anglicky

Reactive oxygen species constantly generated as by-products of cellular metabolism readily attack genomic DNA creating mutagenic lesions such as 7,8-dihydro-8-oxo-guanine (8-oxo-G) that promote aging. 8-oxo-G:A mispairs arising during DNA replication areeliminated by base excision repair initiated by the MutY DNA glycosylase homologue (MUTYH). Here, by using formaldehyde crosslinking in mammalian cell extracts, we demonstrate that the WRN helicase/exonuclease defective in the premature aging disorder Werner syndrome (WS) is recruited to DNA duplex containing an 8-oxo-G:A mispair in a manner dependent on DNA polymerase lambda (Pol lambda) that catalyzes accurate DNA synthesis over 8-oxo-G. Similarly, by immunofluorescence, we show that Pol lambda is required for accumulation of WRN at sites of 8-oxo-G lesions in human cells. Moreover, we show that nuclear focus formation of WRN and Pol lambda induced by oxidative stress is dependent on ongoing DNA replication and on the presence of MUT

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

—

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2012

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

—

Svazek periodika

40

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

8449-8459

Kód UT WoS článku

000309464300033

EID výsledku v databázi Scopus

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