Figure 4.

A model outlining possible steps during homologous recombination where chromatin modifiers regulate the repair/rejection decision. We hypothesize that factors promoting nucleosome assembly/maintenance, such as CAF-1 and Rtt106, deposit nucleosomes at DNA lesions independent of DNA synthesis on ssDNA prior to strand invasion (1). Such deposition/maintenance, coupled with the formation of Sir2-dependent chromatin marks that promote a closed chromatin state, stabilizes D-loops to suppress rejection. Additionally, we hypothesize that CAF-1 physically interacts with Msh6, and possibly Sgs1, to inhibit the rejection factors from unwinding heteroduplex substrates (2). Finally, DNA synthesis-coupled nucleosome deposition by CAF-1 and Rtt106, combined with Sir2-dependent modifications of these nucleosomes (negatively regulated by Rpd3), are likely to stabilize heteroduplex D-loop intermediates, making it more difficult for rejection factors to unwind the intermediates (3). In this model, MSH proteins are recruited to a DSB either directly or through specific histone marks, and nucleosome maintenance limits the time frame in which antirecombination can be performed, and promotes repair of the broken chromosome and ultimately mismatch repair steps (see text for additional details). Factors/steps that promote rejection are highlighted in pink boxes and those that promote repair are highlighted in yellow boxes. DSB, double-strand break; ssDNA, single-stranded DNA; MSH, MutS homolog; STR, Sgs1-Top3-Rmi1.