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Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells
Author(s) -
Abraham Jacinth,
Lemmers Bénédicte,
Hande M.Prakash,
Moynahan Mary Ellen,
Chahwan Charly,
Ciccia Alberto,
Essers Jeroen,
Hanada Katsuhiro,
Chahwan Richard,
Khaw Aik Kia,
McPherson Peter,
Shehabeldin Amro,
Laister Rob,
Arrowsmith Cheryl,
Kanaar Roland,
West Stephen C.,
Jasin Maria,
Hakem Razqallah
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg580
Subject(s) - biology , dna , genomic dna , computational biology , dna damage , genetics , genome instability
Yeast and human Eme1 protein, in complex with Mus81, constitute an endonuclease that cleaves branched DNA structures, especially those arising during stalled DNA replication. We identified mouse Eme1, and show that it interacts with Mus81 to form a complex that preferentially cleaves 3′‐flap structures and replication forks rather than Holliday junctions in vitro . We demonstrate that Eme1 −/− embryonic stem (ES) cells are hypersensitive to the DNA cross‐linking agents mitomycin C and cisplatin, but only mildly sensitive to ionizing radiation, UV radiation and hydroxyurea treatment. Mammalian Eme1 is not required for the resolution of DNA intermediates that arise during homologous recombination processes such as gene targeting, gene conversion and sister chromatid exchange (SCE). Unlike Blm‐deficient ES cells, increased SCE was seen only following induced DNA damage in Eme1‐deficient cells. Most importantly, Eme1 deficiency led to spontaneous genomic instability. These results reveal that mammalian Eme1 plays a key role in DNA repair and the maintenance of genome integrity.