RT Journal Article
SR Electronic
T1 Topoisomerases modulate the timing of meiotic DNA breakage and repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 672337
DO 10.1101/672337
A1 Heldrich, Jonna
A1 Sun, Xiaoji
A1 Vale-Silva, Luis A.
A1 Markowitz, Tovah E.
A1 Hochwagen, Andreas
YR 2019
UL http://biorxiv.org/content/early/2019/06/15/672337.abstract
AB During meiotic prophase, concurrent transcription, recombination, and changes in chromosome morphology place substantial topological strain on chromosomal DNA, but the roles of topoisomerases in this context remain poorly defined. Here, we show that meiotic Saccharomyces cerevisiae chromosomes accumulate topoisomerases primarily in promoter-containing intergenic regions (IGRs) of actively transcribing genes. Wide IGRs exhibit the highest level of meiotic transcription and the strongest topoisomerase buildup. Topoisomerase binding partially overlaps with double-strand break (DSB) hotspots, where the topoisomerase-like enzyme Spo11 initiates meiotic recombination. We show that TOP1 disruption mildly delays DSB induction, whereas a catalytic loss-of-function allele of TOP2 (top2-1) accelerates DSB formation. This acceleration is associated with persistent Top2 on meiotic chromosomes and is not observed upon Top2 depletion. In addition to altering DSB timing, the top2-1 allele also uncouples chromosome synapsis from Pch2/TRIP13-dependent chromosome remodeling and delays DSB repair. Thus, topoisomerase function is required at multiple points to modulate the timing of meiotic recombination.