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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mating-type switching in Schizosaccharomyces pombe involves a strand-specific, alkali-labile imprint at the mat1 (mating-type) locus. The imprint is synthesized during replication in a swi1, swi3, and polymerase alpha (swi7) dependent manner and is dependent on mat1 being replicated in a specific direction. Here we show that the direction of replication at mat1 is controlled by a cis-acting polar terminator of replication (RTS1). Two-dimensional gel analysis of replication intermediates reveals that RTS1 only terminates replication forks moving in the centromere-distal direction. A genetic analysis shows that RTS1 optimizes the imprinting process. Transposing the RTS1 element to the distal side of mat1 abolishes imprinting of the native mat1 allele but restores imprinting of an otherwise unimprinted inverted mat1 allele. These data provide conclusive evidence for the "direction of replication model" that explains the asymmetrical switching pattern of S. pombe, and identify a DNA replication-arrest element implicated in a developmental process. Such elements could play a more general role during development and differentiation in higher eukaryotes by regulating the direction of DNA replication at key loci.
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PMID:A DNA replication-arrest site RTS1 regulates imprinting by determining the direction of replication at mat1 in S. pombe. 1151 38

Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during lagging-strand synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting spacer region important for the imprinting process that affects where subsequent primers are put down after the replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fully-processed Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister chromatids are established during DNA replication through the involvement of replication barriers.
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PMID:Identification of a novel type of spacer element required for imprinting in fission yeast. 2142 20