Identification and molecular characterization of the mammalian α-kleisin RAD21L

Abstract

Meiosis is a fundamental process that generates new combinations between maternal and paternal genomes and haploid gametes from diploid progenitors. Many of the meiosis-specific events stem from the behavior of the cohesin complex (CC), a proteinaceous ring structure that entraps sister chromatids until the onset of anaphase. CCs ensure chromosome segregation, participate in DNA repair, regulate gene expression, and also contribute to synaptonemal complex (SC) formation at meiosis by keeping long-range distant DNA interactions through its conserved structure. Studies from yeast to humans have led to the assumption that Scc1/RAD21 is the α-kleisin that closes the tripartite CC that entraps two DNA molecules in mitosis, while its paralog REC8 is essential for meiosis. Here we describe the identification of RAD21L, a novel mammalian CC subunit with homology to the RAD21/REC8 α-kleisin subfamily, which is expressed in mouse testis. RAD21L interacts with other cohesin subunits such as SMC1α, SMC1b, SMC3 and with the meiosis-specific STAG3 protein. Thus, our results demonstrate the existence of a new meiotic-specific CC constituted by this α-kleisin and expand the view of REC8 as the only specific meiotic α-kleisin.

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

“…Mammalian meiocytes also contain Smc1b, a meiosis-specific ortholog of the mitotic Smc1 (Smc1a), and a paralog of SA1/2, known as STAG3 (McNicoll et al 2013). An additional meiosis-specific a-kleisin subunit, called Rad21L, has recently been identified in mammals and is present primarily during early prophase (Gutierrez-Caballero et al 2011;Ishiguro et al 2011;Lee and Hirano 2011). Meiosisspecific cohesin subunits, together with mitotic subunits, form up to six different cohesin complexes in mammalian meiosis (Lee and Hirano 2011;McNicoll et al 2013).…”

The Roles of Cohesins in Mitosis, Meiosis, and Human Health and Disease

“…Although these three subunits are strictly expressed in germ cells, SMC1α, RAD21, and SA2/STAG2 are also implemented in meiotic chromosome dynamics [97]. Recently, a third kleisin subunit in mammals, named RAD21L, has been identified in meiotic cells and localizes along the AE/LEs of the SC throughout meiosis I [98–101]. This subunit may be involved in synapsis initiation and crossover formation between homologous chromosomes.…”

“…RAD21, like REC8, also appears at the AE/LE during all stages of prophase I [108,109]. RAD21L is expressed from premeiotic S phase and localizes along the AE in leptonema, with some conflicting reports as to whether it persists to midpachynema or diplonema and into metaphase I [98–101]. …”

“…STAG3 is observed along the AE/LE as in leptonema [95]. RAD21L localizes along the AE/LEs in zygonema in a punctate or continuous linear pattern depending on the report [98–101]. …”

“…Although RAD21L is distributed along the SC through at least mid-pachynema, reports of its localization vary. Some groups have reported that RAD21L is evenly distributed along the AE/LE, while other groups have reported that it is discontinuous [98–101]. In addition, two groups have reported that RAD21L localizes in a mutually exclusive pattern with REC8, perhaps suggesting inherent loading sites for these cohesins [100,101].…”