Heterochromatin proteins influence the choice of DNA repair in euchromatin domains

Abstract

In most eukaryotes including the fission yeast, constitutive heterochromatin in pericentromere and telomere domains is marked by methylation of histone H3K9, which provides a binding platform for specialized proteins including heterochromatin protein 1 (HP1). These proteins contribute to transcriptional silencing, cohesion, and kinetochore recruitment. We showed previously that loss of heterochromatin leads to genome rearrangement in the pericentromere repeats that is exacerbated by replication fork destabilization (e.g., Li et al (2013) Cell Rep. 3:638). This indicates that heterochromatin and fork stability make unique contributions to maintain a repetitive domain and resist recombination.Evidence from mammalian systems has implicated heterochromatin proteins in transient response to induced DNA double strand breaks in euchromatin domains. Unexpectedly, we observed that mutants lacking the histone methyltransferase Clr4, or chromodomain proteins Chp1 or Swi6 show evidence of genome instability in euchromatin even in the absence of exogenous damage. Using molecular and cytological approaches, we have investigated the role of these proteins in maintaining euchromatin genome stability in otherwise unperturbed cells, as well as in response to distinct forms of genome stress. We determined that a subset of heterochromatin‐associated proteins contribute to the choice of repair pathway in euchromatin domains by modulating resection of DNA ends. Thus, H3K9 histone methylation and its associated proteins are not limited to heterochromatin domains and influence chromosome stability broadly throughout the genome.Support or Funding InformationSupport by NIH R35 GM118109This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.