BimD/SPO76 is at the interface of cell cycle progression, chromosome morphogenesis, and recombination

Abstract

BIMD of Aspergillus nidulans belongs to a highly conserved protein family implicated, in filamentous fungi, in sister-chromatid cohesion and DNA repair. We show here that BIMD is chromosome associated at all stages, except from late prophase through anaphase, during mitosis and meiosis, and is involved in several aspects of both programs. First, bimD ؉ function must be executed during S through M. Second, in bimD6 germlings, mitotic nuclear divisions and overall cellular program occur more rapidly than in wild type. Thus, BIMD, an abundant chromosomal protein, is a negative regulator of normal cell cycle progression. Third, bimD6 reduces the level of mitotic interhomolog recombination but does not alter the ratio between crossover and noncrossover outcomes. Moreover, bimD6 is normal for intrachromosomal recombination. Therefore, BIMD is probably not involved in the enzymology of recombinational repair per se. Finally, during meiosis, staining of the Sordaria ortholog Spo76p delineates robust chromosomal axes, whereas BIMD stains all chromatin. SPO76 and bimD are functional homologs with respect to their roles in mitotic chromosome metabolism but not in meiosis. We propose that BIMD exerts its diverse influences on cell cycle progression as well as chromosome morphogenesis and recombination by modulating chromosome structure.

Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts

“…Members of the Pds5/BimD/Spo76 family of proteins are present in most eukaryotic organisms and their genetic studies have been described in fungi (Denison et al, 1993;van Heemst et al, 1999;Hartman et al, 2000;Panizza et al, 2000;Tanaka et al, 2001;van Heemst et al, 2001;Wang et al, 2002;Stead et al, 2003) and C. elegans (Wang et al, 2003). Vertebrate cells have two different Pds5-like proteins, and the initial biochemical characterization of only one of them has been reported before (Sumara et al, 2000).…”

“…In contrast, Pds5 is non-essential in Schizosaccharomyces pombe, and a ∆pds5 mutant shows cohesion defects only after prolonged arrest in G2/M (Tanaka et al, 2001;Wang et al, 2002). In Sordaria and Aspergillus, Spo76/BimD is important for both cohesion and condensation in mitosis and meiosis, but to a variable extent (van Heemst et al, 1999;van Heemst et al, 2001). Cohesion defects are also observed during meiosis in Caenorhabditis elegans elv-Sister chromatid cohesion is essential for proper segregation of the genome in mitosis and meiosis.…”

Intra-G 1 arrest in response to UV irradiation in fission yeast

“…Among these, two are particularly striking. First, there are several reports that G 1 ͞S progression is regulated, positively or negatively, by chromosomal proteins that originally were identified by their roles in meiotic or mitotic sister chromatid cohesion or meiotic interhomolog interactions, none of which can take place in mitotic G 1 cells (48)(49)(50)(51)(52)(53)(54). The human homologs of these proteins, the chromosome morphogenesis protein Spo76͞BIMD͞AS3 and the securin Pds1͞Cut2, are both implicated as tumor suppressor proteins, and modulation of progression through G 1 by these proteins can be directly linked to cancer (51,52).…”

A mechanical basis for chromosome function

“…Information might then flow from the chromosomes to the cell cycle engine. Such ''reverse information flow'' could explain diverse powerful effects of altered histone modification on cell cycle progression and modulation of G 1 ͞S progression by chromosome structure proteins (15,37). Intrinsic chromatin stress cycling could also explain situations where chromosome output varies cyclically irrespective of the cell cycle engine (38)(39)(40).…”