Meiosis is the cell division program producing haploid gametes from diploid precursor cells. A key step during meiosis is crossover (CO) formation, which results in physical attachments between homologous chromosomes that are critical for their accurate segregation at meiosis I. In C. elegans, a single CO is formed per homolog pair and it is located on the terminal thirds of most chromosomes. The off-centered position of the CO has been proposed to dictate the cruciform shape acquired by bivalents during late prophase chromosome remodeling resulting in short and long chromosome arms. The bias towards off-centered COs is also observed in human and mouse male meiosis. Furthermore, in human female meiosis, COs occurring near telomeres are thought to contribute to aneuploidy and are usually suppressed. However, a direct analysis as to whether and how the position of the CO is a major determinant of late prophase chromosome remodeling has not been previously done in metazoans. Here, we are addressing these important questions by using an inducible single DNA double-strand break (DSB) system based on Mos1 transposon excision in spo-11 mutants, which lack endogenous meiotic DSBs. We found that induction of a DSB resulting in a CO at the center of chromosome III fails to restrict LAB-1 (the functional analog of Shugoshin) to the long arms, and that both AIR-2 (Aurora B kinase) and SYP-1 (central region component of the synaptonemal complex) no longer exhibit a constrained localization to the short arms of the reconstituted bivalent. The short/long arm identities can be restored by exogenous DSB formation via gamma-IR suggesting that off-centered DSBs are a preferred substrate for CO formation. This is further supported by analysis in rec-1 mutants where DSBs are SPO-11 derived, eliminating the concern of a Mos1 artifact, but where CO distribution is biased towards to the center of the chromosomes, and normal short/long arm identities also fail to be established. Finally, inducing a single DSB at a telomere on chromosome III fails to form bivalents indicating that terminally located COs are either suppressed or fail to sustain a physical attachment between homologs. Together, these findings demonstrate that CO position directs late prophase chromosome remodeling. Ongoing analysis of single DSBs induced on other chromosomes and at different chromosome positions suggests a mechanism in which distances are measured from the CO site to chromosome ends dictating short/long chromosome arm identity.
Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
The Genetics Society of America
9650 Rockville Pike, Bethesda, MD
Phone: 301-634-7300, Fax: 301-634-7079
Questions and Comments: firstname.lastname@example.org