BURKOVICS, Peter, Lili DOME, Szilvia JUHASZ, Veronika ALTMANNOVÁ, Marek ŠEBESTA, Martin PAČESA, Kasper FUGGER, Claus Storgaard SORENSEN, Marietta Y.W.T. LEE, Lajos HARACSKA a Lumír KREJČÍ. The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis. Nucleic Acids Research. Oxford: Oxford University Press, 2016, roč. 44, č. 7, s. 3176-3189. ISSN 0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkw024. |
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@article{1355901, author = {Burkovics, Peter and Dome, Lili and Juhasz, Szilvia and Altmannová, Veronika and Šebesta, Marek and Pačesa, Martin and Fugger, Kasper and Sorensen, Claus Storgaard and Lee, Marietta Y.W.T. and Haracska, Lajos and Krejčí, Lumír}, article_location = {Oxford}, article_number = {7}, doi = {http://dx.doi.org/10.1093/nar/gkw024}, keywords = {CELL NUCLEAR ANTIGEN; UBIQUITIN-BINDING DOMAINS; DAMAGE TOLERANCE PATHWAY; BLOOMS-SYNDROME HELICASE; SACCHAROMYCES-CEREVISIAE; REPLICATION FORK; POSTREPLICATION REPAIR; TRANSLESION SYNTHESIS; GENOMIC STABILITY; SUMO MODIFICATION}, language = {eng}, issn = {0305-1048}, journal = {Nucleic Acids Research}, title = {The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis}, volume = {44}, year = {2016} }
TY - JOUR ID - 1355901 AU - Burkovics, Peter - Dome, Lili - Juhasz, Szilvia - Altmannová, Veronika - Šebesta, Marek - Pačesa, Martin - Fugger, Kasper - Sorensen, Claus Storgaard - Lee, Marietta Y.W.T. - Haracska, Lajos - Krejčí, Lumír PY - 2016 TI - The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis JF - Nucleic Acids Research VL - 44 IS - 7 SP - 3176-3189 EP - 3176-3189 PB - Oxford University Press SN - 03051048 KW - CELL NUCLEAR ANTIGEN KW - UBIQUITIN-BINDING DOMAINS KW - DAMAGE TOLERANCE PATHWAY KW - BLOOMS-SYNDROME HELICASE KW - SACCHAROMYCES-CEREVISIAE KW - REPLICATION FORK KW - POSTREPLICATION REPAIR KW - TRANSLESION SYNTHESIS KW - GENOMIC STABILITY KW - SUMO MODIFICATION N2 - Successful and accurate completion of the replication of damage-containing DNA requires mainly recombination and RAD18-dependent DNA damage tolerance pathways. RAD18 governs at least two distinct mechanisms: translesion synthesis (TLS) and template switching (TS)-dependent pathways. Whereas TS is mainly error-free, TLS can work in an error-prone manner and, as such, the regulation of these pathways requires tight control to prevent DNA errors and potentially oncogenic transformation and tumorigenesis. In humans, the PCNA-associated recombination inhibitor (PARI) protein has recently been shown to inhibit homologous recombination (HR) events. Here, we describe a biochemical mechanism in which PARI functions as an HR regulator after replication fork stalling and during double-strand break repair. In our reconstituted biochemical system, we show that PARI inhibits DNA repair synthesis during recombination events in a PCNA interaction-dependent way but independently of its UvrD-like helicase domain. In accordance, we demonstrate that PARI inhibits HR in vivo, and its knockdown suppresses the UV sensitivity of RAD18-depleted cells. Our data reveal a novel human regulatory mechanism that limits the extent of HR and represents a new potential target for anticancer therapy. ER -
BURKOVICS, Peter, Lili DOME, Szilvia JUHASZ, Veronika ALTMANNOVÁ, Marek ŠEBESTA, Martin PAČESA, Kasper FUGGER, Claus Storgaard SORENSEN, Marietta Y.W.T. LEE, Lajos HARACSKA a Lumír KREJČÍ. The PCNA-associated protein PARI negatively regulates homologous recombination via the inhibition of DNA repair synthesis. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2016, roč.~44, č.~7, s.~3176-3189. ISSN~0305-1048. Dostupné z: https://dx.doi.org/10.1093/nar/gkw024.
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