Genetic evidence for functional interaction of Smc5/6 complex and Top1 with spatial frequency of replication origins required for maintenance of chromosome stability

Rai, Ragini and Laloraya, Shikha (2017) Genetic evidence for functional interaction of Smc5/6 complex and Top1 with spatial frequency of replication origins required for maintenance of chromosome stability. In: CURRENT GENETICS, 63 (4). pp. 765-776.

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Abstract

Replication of linear chromosomes is facilitated by firing of multiple replication origins that ensures timely duplication of the entire chromosome. The Smc5/6 complex is thought to play an important role in replication by its involvement in the restart of collapsed replication forks. Here, we present genetic evidence for functional interaction between replication origin distribution and two subunits of the Smc5/6 complex, Smc6 and Mms21, as well as Top1. An artificial chromosome that has a long arm having low origin density (5ori Delta YAC) is relatively unstable compared to the YAC having normal origin distribution in wild-type cells, but is partially stabilized in smc6-56 and top1 Delta mutants. While a SUMO-ligase-deficient mutant of Mms21 does not affect stability of the 5ori Delta YAC by itself, in combination with top1 Delta, the 5ori Delta YAC is destabilized as evidenced by increased chromosome loss frequency in the mms21 Delta sl top1 Delta double mutant. Likewise, the smc6-56 top1 Delta double mutant also exhibits enhanced destabilization of the 5ori Delta YAC compared to either single mutant. Such an increase in chromosome loss is not observed for a similar YAC that retains the original replication origins and normal origin distribution on the long arm, in either double mutant having the mms21 Delta sl or smc6-56 mutations in combination with top1 Delta. Our findings reveal a requirement for the Smc5/6 complex, including Mms21/Nse2 mediated sumoylation, and topoisomerase-1 (Top1), for maintaining stability of a chromosome having low origin density and suggest a functional cooperation between the Smc5/6 complex and Top1 in maintenance of topologically challenged chromosomes prone to replication fork collapse or accumulation of torsional stress.

Item Type:	Journal Article
Publication:	CURRENT GENETICS
Additional Information:	Copy right for this article belongs to the SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	03 Aug 2017 10:17
Last Modified:	03 Aug 2017 10:17
URI:	http://eprints.iisc.ac.in/id/eprint/57567

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