biostudies-literatureUnknown41(19)Saugar IThe structure-specific Mus81-Eme1/Mms4 endonuclease contributes importantly to DNA repair and genome integrity maintenance. Here, using budding yeast, we have studied its function and regulation during the cellular response to DNA damage and show that this endonuclease is necessary for successful chromosome replication and cell survival in the presence of DNA lesions that interfere with replication fork progression. On the contrary, Mus81-Mms4 is not required for coping with replicative stress originated by acute treatment with hydroxyurea (HU), which causes fork stalling. Despite its requirement for dealing with DNA lesions that hinder DNA replication, Mus81-Mms4 activation is not induced by DNA damage at replication forks. Full Mus81-Mms4 activity is only acquired when cells finish S-phaNucleic acids research8943-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC3799426biostudies-literatureTemporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage.PMC3799426Calzada ASaugar IVazquez MVOrtiz-Bazan MASegurado MGallo-Fernandez MTercero JAfalseTemporal regulation of the Mus81-Mms4 endonuclease ensures cell survival under conditions of DNA damage.The structure-specific Mus81-Eme1/Mms4 endonuclease contributes importantly to DNA repair and genome integrity maintenance. Here, using budding yeast, we have studied its function and regulation during the cellular response to DNA damage and show that this endonuclease is necessary for successful chromosome replication and cell survival in the presence of DNA lesions that interfere with replication fork progression. On the contrary, Mus81-Mms4 is not required for coping with replicative stress originated by acute treatment with hydroxyurea (HU), which causes fork stalling. Despite its requirement for dealing with DNA lesions that hinder DNA replication, Mus81-Mms4 activation is not induced by DNA damage at replication forks. Full Mus81-Mms4 activity is only acquired when cells finish S-pha2013-01-01T00:00:00Z2013 Oct2025-04-04T19:29:42.513Z2019-03-27T01:17:17ZS-EPMC37994262390101010.1093/nar/gkt645