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Genome‐wide replication profiles of S‐phase checkpoint mutants reveal fragile sites in yeast
Author(s) -
Raveendranathan Miruthubashini,
Chattopadhyay Sharbani,
Bolon YungTsi,
Haworth Justin,
Clarke Duncan J,
Bielinsky AnjaKatrin
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601251
Subject(s) - biology , genetics , genome , replication (statistics) , g2 m dna damage checkpoint , saccharomyces cerevisiae , mutant , yeast , chromosomal fragile site , schizosaccharomyces , dna replication , fungal protein , computational biology , gene , schizosaccharomyces pombe , cell cycle checkpoint , cell cycle , virology , chromosome
The S‐phase checkpoint kinases Mec1 and Rad53 in the budding yeast, Saccharomyces cerevisiae , are activated in response to replication stress that induces replication fork arrest. In the absence of a functional S‐phase checkpoint, stalled replication forks collapse and give rise to chromosome breakage. In an attempt to better understand replication dynamics in S‐phase checkpoint mutants, we developed a replication origin array for budding yeast that contains 424 of 432 previously identified potential origin regions. As expected, mec1‐1 and rad53‐1 mutants failed to inhibit late origin activation. Surprisingly however, 17 early‐firing regions were not replicated efficiently in these mutants. This was not due to a lack of initiation, but rather to problems during elongation, as replication forks arrested in close proximity to these origins, resulting in the accumulation of small replication intermediates and eventual replication fork collapse. Importantly, these regions were not only prone to chromosome breakage in the presence of exogenous stress but also in its absence, similar to fragile sites in the human genome.