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            <title xml:lang="en">Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends</title>
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              <persName>
                <forename type="first">Josée</forename>
                <surname>Guirouilh-Barbat</surname>
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                <forename type="first">Emilie</forename>
                <surname>Rass</surname>
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              <persName>
                <forename type="first">Isabelle</forename>
                <surname>Plo</surname>
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              <persName>
                <forename type="first">Pascale</forename>
                <surname>Bertrand</surname>
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              <email type="md5">6adaaddf03c967a449e5ff2fc8d9aeb7</email>
              <email type="domain">cea.fr</email>
              <idno type="idhal" notation="numeric">834707</idno>
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              <idno type="ORCID">https://orcid.org/0000-0002-9019-742X</idno>
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            <author role="aut">
              <persName>
                <forename type="first">Bernard</forename>
                <forename type="middle">S.</forename>
                <surname>Lopez</surname>
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                <forename>Josée</forename>
                <surname>Guirouilh-Barbat</surname>
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              <email type="md5">eb837f1cfbce9aec171ed23e3c39e83f</email>
              <email type="domain">cnrs.fr</email>
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            <funder>This work is supported by a La Ligue Nationale contre le Cancer fellowship (E.R.), La Ligue Nationale contre le Cancer “Equipes labellisées, La Ligue 2005,” Agence Nationale de la Recherche, and Institut National du Cancer.</funder>
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              <date type="whenSubmitted">2020-12-09 11:18:46</date>
              <date type="whenModified">2026-03-31 03:03:58</date>
              <date type="whenReleased">2020-12-09 11:18:46</date>
              <date type="whenProduced">2007-12-26</date>
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            <idno type="halRefHtml">&lt;i&gt;Proceedings of the National Academy of Sciences of the United States of America&lt;/i&gt;, 2007, 104 (52), pp.20902-20907. &lt;a target="_blank" href="https://dx.doi.org/10.1073/pnas.0708541104"&gt;&amp;#x27E8;10.1073/pnas.0708541104&amp;#x27E9;&lt;/a&gt;</idno>
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            <idno type="stamp" n="CEA">CEA - Commissariat à l'énergie atomique</idno>
            <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
            <idno type="stamp" n="IGR" corresp="FNCLCC">Institut Gustave Roussy</idno>
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                <title xml:lang="en">Defects in XRCC4 and KU80 differentially affect the joining of distal nonhomologous ends</title>
                <author role="aut">
                  <persName>
                    <forename type="first">Josée</forename>
                    <surname>Guirouilh-Barbat</surname>
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                  <idno type="IDREF">https://www.idref.fr/202758001</idno>
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                <author role="aut">
                  <persName>
                    <forename type="first">Emilie</forename>
                    <surname>Rass</surname>
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                  <idno type="idhal" notation="numeric">1317619</idno>
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                <author role="aut">
                  <persName>
                    <forename type="first">Isabelle</forename>
                    <surname>Plo</surname>
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                  <idno type="IDREF">https://www.idref.fr/068888376</idno>
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                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Pascale</forename>
                    <surname>Bertrand</surname>
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                  <email type="md5">6adaaddf03c967a449e5ff2fc8d9aeb7</email>
                  <email type="domain">cea.fr</email>
                  <idno type="idhal" notation="numeric">834707</idno>
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                  <idno type="ORCID">https://orcid.org/0000-0002-9019-742X</idno>
                  <affiliation ref="#struct-513"/>
                </author>
                <author role="aut">
                  <persName>
                    <forename type="first">Bernard</forename>
                    <forename type="middle">S.</forename>
                    <surname>Lopez</surname>
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                  <email type="md5">6ddb8edbd120feca83e5cb6590b2e57d</email>
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                  <idno type="idhal" notation="string">bernard-lopez</idno>
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                <idno type="halJournalId" status="VALID">7969</idno>
                <idno type="issn">0027-8424</idno>
                <idno type="eissn">1091-6490</idno>
                <title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
                <imprint>
                  <publisher>National Academy of Sciences</publisher>
                  <biblScope unit="volume">104</biblScope>
                  <biblScope unit="issue">52</biblScope>
                  <biblScope unit="pp">20902-20907</biblScope>
                  <date type="datePub">2007-12-26</date>
                  <date type="dateEpub">2007-12-26</date>
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              <idno type="doi">10.1073/pnas.0708541104</idno>
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              <classCode scheme="halDomain" n="sdv.gen.gh">Life Sciences [q-bio]/Genetics/Human genetics</classCode>
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            <abstract xml:lang="en">
              <p>XRCC4-null mice have a more severe phenotype than KU80-null mice. Here, we address whether this difference in phenotype is connected to nonhomologous end-joining (NHEJ). We used intrachromosomal substrates to monitor NHEJ of two distal double-strand breaks (DSBs) targeted by I-SceI, in living cells. In xrcc4-defective XR-1 cells, a residual but significant end-joining process exists, which primarily uses microhomologies distal from the DSB. However, NHEJ efficiency was strongly reduced in xrcc4-defective XR-1 cells versus complemented cells, contrasting with KU-deficient xrs6 cells, which showed levels of end-joining similar to those of complemented cells. Nevertheless, sequence analysis of the repair junctions indicated that the accuracy of end-joining was strongly affected in both xrcc4-deficient and KU-deficient cells. More specifically, these data showed that the KU80/XRCC4 pathway is conservative and not intrinsically error-prone but can accommodate non-fully complementary ends at the cost of limited mutagenesis.</p>
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