Telomere-promoted rapid prophase movements in meiotic prophase first appear in early leptotene as an increase in translation of telomeres across the nuclear envelope, without a concomitant increase in the average speed of movement even though there are occasional, brief movements that are faster than seen in vegetative cells (). These early RPMs foster interactions between heterologous as well as between homologous chromosomes, independent of meiotic recombination and prior to zygotene (). Two mps3
mutants with defects in RPMs intermediate between wild-type and ndj1
Δ also have intermediate chromosome pairing rates (, , ) and in general have intermediate rates of sporulation and spore viability, disomic spore production, premature sister chromatid separation and, for mps3-dAR
, delay prior to anaphase I (). Among RPM mutants with a range of delays in completing synapsis, as in wild-type, we consistently observe that shorter chromosomes are the last to synapse (). Given that (1) recombination generally is not reduced in RPM mutants, and (2) the normal mechanisms that lead to synapsis are likely intact 
, we conclude that the delay in synapsis results primarily from a delay in pairing, consistent with prior work similarly supporting a role in pairing for Ndj1 
and Csm4 
Immunocytological examination suggests that the common defect among the various RPM mutants is that telomeres do not engage cytoplasmic motors as in wild-type cells, either because attachments to the SUN-protein bridge across the nuclear envelope are weakened (ndj1
; ), the bridge itself is defective (mps3-dCC
) or the motors associated with the cytoskeleton are somehow rendered ineffective (csm4
Δ). Surprisingly, as assayed here formation of the bouquet appears to be equally defective in the various RPM mutants (). It is particularly informative that pairing in mps3-dCC
appears only slightly delayed, (), suggesting that the bouquet makes at most a small contribution to pairing in budding yeast. Rather, the kinetics of pairing are strongly correlated with the ability of the telomere-led movements to change the locations of the chromosomes within the nucleus. We suggest that telomere translation along the nuclear envelope is the critical feature of the SUN protein-promoted movements, in part because deformations of the yeast nucleus reported by others 
are relatively mild and infrequent in our strains. In mps3-dNT
Δ, where movements are equivalent to the level in mitotic cells 
, pairing and synapsis presumably are aided by movement from activities such as thermal motion, chromatin remodeling, DNA and RNA metabolism, and polymerization/depolymerization of intranuclear microtubules that might displace chromatin.
We anticipated a pairing function for RPMs 
and, with others, suggested that RPMs may in addition promote destabilization of inappropriate interactions, entanglements and/or interlocks 
. We have not observed interlocked chromosomes in our spread preparations. Furthermore, longer chromosomes would seem more susceptible than short chromosomes to entanglements and interlocks, and a defect in resolving these problems could be expected to delay long chromosome pairing and/or synapsis disproportionately. However we have observed that smaller chromosomes are the last chromosomes to pair and synapse in the RPM mutants (or perhaps never do synapse, as chromosomes that lack crossovers in ndj1
Δ are the shorter ones - see Table S7 in 
). The simplest interpretation is that RPMs primarily influence pairing and synapsis not by resolving interlocks but by extending the range of the homology search. Nevertheless, interlocks may be difficult to visualize in budding yeast and, furthermore, we cannot rule out the possibility that RPMs contribute to interlock formation by promoting telomere-proximal recombination at an early stage and then contribute to interlock resolution by continued movement at later stages. It also remains possible that RPMs disengage less cytologically evident entanglements, such as entanglements between chromosome axes which are resolved prior to the onset of synapsis or entanglements of loops of chromatin of different chromosomes, which would not involve the chromosome axes 
Conservation of the bouquet suggests conserved function and, given the timing of bouquet formation it is not surprising that a role for the bouquet in pairing is widely accepted. A complicating factor for earlier work is that prior to the recognition that telomere-led RPMs are well-conserved, bouquet formation appeared to be the primary defect in a variety of mutants with pairing and synapsis defects, a good example being ndj1
Δ where it now appears that the RPM defect is primary, with bouquet and pairing defects being secondary. Fission yeast, which has provided the clearest data in support of a role for the bouquet in pairing and recombination, also has provided the clearest data for a role for the bouquet in SPB stability and spindle function in the first meiotic division 
. The sporulation and spore viability defects in mps3-dCC
could reflect a direct impact of the mutation on spindle pole body function per se
, given that the defects in RPMs and chromosome segregation are mild or absent (). However, we have observed no defects in vegetative growth in mps3-dCC
, and it is possible that absence of the bouquet in mps3-dCC
specifically causes the later problems.
Specifically how RPMs function to promote pairing in combination with the recombination-directed homology search is an open question. Following the DNA double-strand break (DSB) formation that launches meiotic recombination, resection creates single-stranded DNA that is coated with recA
-like enzymes which then promote invasion of homologous DNA, this last step presumably insuring that pairing is homology-dependent. The farther the single-strand end can diffuse away from the axis of the chromosome, the less dependent on active whole-chromosome movement this part of the search would become, although presumably the potential for entanglements would increase as well. Reliance of timely pairing and synapsis on RPMs suggests that the single-strand extension search volume is limiting. A simple model for the role of RPMs early in prophase is that RPMs promote collisions by generating relatively random long-range chromosome movements, thus increasing the probability that a single-stranded end will encounter homologous DNA 
; this process might be particularly important for short chromosomes that cannot reach across the nucleus when telomeres are tethered to the nuclear envelope ().
Model for RPM contribution to pairing.
The meiotic delay associated with defective RPMs leads to negative consequences for the cell, although the mechanism is not certain. One possibility is that the pairing delay leads to continued resection which might help promote the homology search by extending the search radius but at a cost of increased entangling and/or possibly of increased ectopic recombination 
. Alternatively, checkpoint adaptation before recombination is sufficiently complete could lead to chromosome missegregation, or depletion of energy stores during the prolonged prophase could prevent completion of sporulation. Whether RPMs play additional roles in meiotic chromosome metabolism remains to be determined but their conservation across phyla indicates that RPMs are critical for normal meiotic outcomes and fertility.