title: The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair by sister chromatid recombination in Saccharomyces cerevisiae.
abstract: Genomic integrity is threatened by multiple sources of DNA damage. DNA double-strand breaks (DSBs) are among the most dangerous types of DNA lesions and can be generated by endogenous or exogenous agents, but they can arise also during DNA replication. Sister chromatid recombination (SCR) is a key mechanism for the repair of DSBs generated during replication and it is fundamental for maintaining genomic stability. Proper repair relies on several factors, among which histone modifications play important roles in the response to DSBs. Here, we study the role of the histone H3K79 methyltransferase Dot1 in the repair by SCR of replication-dependent HO-induced DSBs, as a way to assess its function in homologous recombination. We show that Dot1, the Rad9 DNA damage checkpoint adaptor, and phosphorylation of histone H2A (gammaH2A) are required for efficient SCR. Moreover, we show that Dot1 and Rad9 promote DSB-induced loading of cohesin onto chromatin. We propose that recruitment of Rad9 to DSB sites mediated by gammaH2A and H3K79 methylation contributes to DSB repair via SCR by regulating cohesin binding to damage sites. Therefore, our results contribute to an understanding of how different chromatin modifications impinge on DNA repair mechanisms, which are fundamental for maintaining genomic stability.
authors.affiliation: Universidad de Salamanca, Salamanca, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Conde
authors.forename: Esther
authors.initials: E
authors.lastname: Refolio
authors.forename: Violeta
authors.initials: V
authors.lastname: Cordón-Preciado
authors.forename: Felipe
authors.initials: F
authors.lastname: Cortés-Ledesma
authors.forename: Luis
authors.initials: L
authors.lastname: Aragón
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
authors.forename: Pedro A
authors.initials: PA
authors.lastname: San-Segundo