Mrc1 marks early-firing origins and coordinates timing and efficiency of initiation in fission yeast.

Abstract:

:How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1Δ cells (and in swi1Δ cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1Δ cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein.

journal_name

Mol Cell Biol

authors

Hayano M,Kanoh Y,Matsumoto S,Masai H

doi

10.1128/MCB.01239-10

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

2380-91

issue

12

eissn

0270-7306

issn

1098-5549

pii

MCB.01239-10

journal_volume

31

pub_type

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