Academic journal article Genetics

Mitotic and Meiotic Functions for the SUMOylation Pathway in the Caenorhabditis Elegans Germline

Academic journal article Genetics

Mitotic and Meiotic Functions for the SUMOylation Pathway in the Caenorhabditis Elegans Germline

Article excerpt

THE Caenorhabditis elegans germline is a dynamic organ that contains both mitotically dividing nuclei and nuclei undergoing meiosis (Hubbard 2005). The distal tip of hermaphroditic gonads contains mitotic nuclei that transition into meiosis, the process by which eggs and sperm are formed. Meiosis involves two rounds of cellular division; the first is reductional and the second equational. Meiosis initiates when homologous chromosomes pair and the synaptonemal complex (SC), a proteinaceous zipper-like structure, forms to hold homologs together (Dernburg et al. 1998; Plug et al. 1998; Walker and Hawley 2000). At this early stage of meiosis, SPO-11 forms DNA double-stranded breaks (DSBs) as the first step in homologous recombination (HR) (Klapholz et al. 1985; Cao et al. 1990; Malone et al. 1991; Keeney et al 1997; McKim and Hayashi-Hagihara 1998; Romanienko and Camerini-Otero 1999). These DSBs are initially processed by the MRE11, RAD50, and NBS1/Xrs2 (MRN/X) complex. RAD-50's coiled-coil and hook domains hold the broken ends together, while MRE11 binds DNA, nicks the DNA upstream of SPO11, and resects the DNA leaving a short 3' overhang (Usui et al. 1998; de Jager et al. 2001; Borde et al. 2004; Milman et al. 2009; Hohl et al. 2011). The latter activity of the MRN/X complex removes SPO11 bound to the 5' end of the DNA and is required for long-range resection performed by other nucleases. The single-stranded binding protein RPA initially covers the single-stranded DNA (ssDNA), and then is replaced by the recombinase RAD51 and/or its meiosis-specific ortholog DMC1 (Bishop et al. 1992; Shinohara et al. 1992; Bishop 1994; Habu et al. 1996; Dresser etal. 1997; Yoshidaetal. 1998). MSH4/5 then localizes to sites that will become interfering crossovers along with other crossover-promoting proteins, including COSA-1 in worms (Hollingsworth et al. 1995; Paquis-Flucklinger et al. 1997; Bocker et al. 1999; Novak et al. 2001; Snowden et al. 2004; Yokoo et al. 2012). Following crossover formation, chromosomes restructure, while the SC disassembles. Chiasmata (the physical manifestation of crossovers) hold the chromosomes together through the end of diakinesis (Rasmussen and Holm 1984; Lawrie et al. 1995; Moens and Spyropoulos 1995; Bascom-Slack et al. 1997).

Although the function of many meiotic proteins is understood, the complex regulation of HR is still under investigation. Many of the canonical HR proteins are modified post-translationally, by phosphorylation, ubiquitination, or SUMOylation (Falck et al. 2012; Lu et al. 2012; Bologna et al. 2015; Ismail et al. 2015; Parameswaran et al. 2015; Luo et al. 2016; Silva et al. 2016; Tomimatsu et al. 2017). SUMOylation is a modification that involves the transfer of a small polypeptide called small ubiquitin-like modifier (SUMO) to a target protein (Choudhury and Li 1997; Lapenta et al. 1997; Mahajan et al. 1997; Chen et al. 1998; Huang et al. 1998; Tanaka et al. 1999). Yeast and C. elegans have a single SUMO moiety, while mammals have three SUMO isoforms (Su and Li 2002). SUMOylation is used to modify protein function; it can be used to stabilize protein complexes, localize target proteins to specific cell organelles, or signal for degradation (similar to ubiquitination). The SUMOylation pathway consists of an E1 activating enzyme that binds SUMO (Haas et al. 1982). E1 then transfers SUMO to an E2 conjugating enzyme, which can transfer SUMO directly to a target protein (Bernier-Villamor et al. 2002). Alternatively, E2 can transfer SUMO to an E3 ligase that then SUMOylates the target protein (Yunus and Lima 2009). C. elegans uses the E1 enzymes UBA-2 and AOS-1, a single E2 enzyme UBC-9, and two canonical E3 ligases GEI-17 and ZK1248.11 (Holway et al. 2006; Pelisch and Hay 2016). A target protein can be monoSUMOylated, or polySUMOylated (Rojas-Fernandez et al. 2014; Horigome et al. 2016). The latter can be branched or straight depending on context. SUMO chains can help create larger structures that may hold macromolecules together in vivo (Tatham et al. …

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