Homologous Recombination Chapter 10 Homologous Recombination 25 and 27 September, 2006

Overview Homologous recombination relies on regions of nearly identical sequence. The Holliday model of the mechanism of recombination involves recognition, strand invasion, branch migration, and resolution. The Double-strand Break Repair model is similar, but involves two Holliday junctions. Homologous recombination is mediated by protein enzymes. RecA (Rad51p) pairs homologous regions and promotes strand exchange. RecBCD (Rad 50/58/60p; MRXp) generates single strand for invasion. RuvAB and RuvC (?) promote branch migration and resolution. Homologous recombination is required for successful meiosis. In meiosis, Spo11 generates DSB, MRXp extends the break, and Rad51 promotes strand invasion. Some events, including mating-type switching in yeast and VDJ recombination involve regulated, specific recombination.

Holliday Junction Cleavage and Strand Invasion

Holliday Resolution

DSB Recombination

DNA Damage leads to DSB

RecBCD and Chi Sites

Chi Site Polarity

RecA-catalyzed Strand Exchange

RecA - DNA Structures

Polarity of Cooperative RecA Binding

Mechanism of RecA Strand Exchange

RuvAB and Branch Migration

RuvC Resolves Holliday Structures

Meiotic Recombination

Spo11p forms Double-stranded Breaks

Recombination Mechanism

Mating-Type Conversion

The mechanism of mating-type conversion involves replication to bring about gene conversion.

Genetic and Physical Maps

Gene Conversion by Mismatch Repair

Resolving Paired Holliday Structures