Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84112, USA-
Abstract: Chromatin-modifying factors regulate both transcription and DNA replication- The yFACT chromatin-reorganizing complex is involved in both processes, and the sensitivity of some yFACT mutants to the replication inhibitor hydroxyurea -HU- is one indication of a replication role- This HU sensitivity can be suppressed by disruptions of the SET2 or CHD1 genes, encoding a histone H3-K36- methyltransferase and a chromatin remodeling factor, respectively- The additive effect of set2 and chd1 mutations in suppressing the HU sensitivity of yFACT mutants suggests that these two factors function in separate pathways- The HU suppression is not an indirect effect of altered regulation of ribonucleotide reductase induced by HU- set2 and chd1 mutations also suppress the HU sensitivity of mutations in other genes involved in DNA replication, including CDC2, CTF4, ORC2, and MEC1- Additionally, a chd1 mutation can suppress the lethality normally caused by disruption of either MEC1 or RAD53 DNA damage checkpoint genes, as well as the lethality seen when a mec1 sml1 mutant is exposed to low levels of HU- The pob3 defect in S-phase progression is suppressed by set2 or chd1 mutations, suggesting that Set2 and Chd1 have specific roles in negatively regulating DNA replication-