Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes

Bloom's syndrome (BS) is a rare autosomal recessive disorder of humans char acterized by severe pre- and postnatal growth deficiency, immunodeficiency, genomic instability, and a predisposition to a wide variety of neoplasms, The genomic instability is evidenced in BS somatic cells as a high incidenc e of gaps and breaks, chromatid exchanges, chromosome rearrangements, and l ocus-specific mutations. BS arises from a mutation in BLM, a gene encoding a protein with homology to the RecQ helicase family. Men with BS are steril e; women have reduced fertility and a shortened reproductive span. The curr ent immunocytological study on mouse spermatocytes shows that the BLM prote in is first evident as discrete foci along the synaptonemal complexes (SCs) of homologously synapsed autosomal bivalents in late zygonema of meiotic p rophase, BLM foci progressively dissociate from the synapsed autosomal axes during early pachynema and are no longer seen in mid-pachynema. BLM coloca lizes with the single-stranded DNA binding replication protein A, which has been shown to be involved in meiotic synapsis. However, there is a tempora l delay in the appearance of BLM protein along the SCs relative to replicat ion protein A, suggesting that BLM is required for a late step in processin g of a subset of genomic DNA involved in establishment of interhomologue in teractions in early meiotic prophase, In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin mo st intimately associated with the SCs, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome d isjunction during anaphase I.