Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex

Abstract

Chromosome organization, dynamics and stability are required for successful passage through cellular generations and transmission of genetic information to offspring. The key components involved are Structural maintenance of chromosomes (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin complex chromosome condensation and the SMC5/6 complex is specialized in the maintenance of genome stability. Here we summarize recent knowledge on the composition and molecular functions of SMC5/6 complex. SMC5/6 complex was originally identified based on the sensitivity of its mutants to genotoxic stress but there is increasing number of studies demonstrating its roles in the control of DNA replication, sister chromatid resolution and genomic location-dependent promotion or suppression of homologous recombination. Some of these functions appear to be due to a very dynamic interaction with cohesin or other repair complexes. Studies in Arabidopsis indicate that, besides its canonical function in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating plant development, abiotic stress responses, suppression of autoimmune responses and sexual reproduction.

Keywords: DNA damage repair; SMC5/6; Structural maintenance of chromosomes; chromatin; chromosomes; genome stability.

Figure 1

Structural maintenance of chromosomes (SMC) 5/6 complex composition and functions. (A) Consensual model of SMC5/6 complex without and (B) with species-specific positions of NON-SMC ELEMENT (NSE) 5(-like) and NSE6(-like) subunits in Schizosaccharomyces pombe, Saccharomyces cerevisiae, Arabidopsis thaliana and Homo sapiens. (C) Hypothetical function of NSE5-NSE6 dimer in multimerizing SMC5/6 complexes via their heads (top) or hinges (bottom). (D) Replication intermediate structure bypassing DNA damage site (red square). (E) Topological stress occurring during DNA replication and at replication fork barriers (RFBs) represented by the positive supercoil (+SC) ahead of the replication fork and sister chromatid intertwining (SCIs) between the nascent chromatids. (F) Role of SMC5/6 complex in telomere length maintenance. (G) Speculative model for SUMOylation of transcriptional modulations by SMC5/6 complex. Note that the position of SMC5/6 complex in images (C), (E), (F) and (G) is only speculative.

Figure 2

Structural maintenance of chromosomes (SMC) 5/6 complex in plants. (A) Log2 mRNA intensity values of genes encoding SMC5/6 complex in 49 Arabidopsis developmental stages. The primary ATH1 expression array data were derived from AtGenExpress dataset [93]. Please note that the NSE1 and NSE4A are missing on ATH1 array. (B) Overview of SMC5/6 complex functions in Arabidopsis.