Division of labor of the replication fork protection complex subunits in sister chromatid cohesion and Chk1 activation

During meiosis, chromosomes acquire unique features: the two pairs of sister chromatids form axial elements (Aes) that synapse and form the synaptonemal complex (sC), telo-meres attach to the nuclear membrane where they form a cluster that later disassembles, meiotic recombination between the two pairs of sister chromatids happens and chiasmata are formed as an obligatory structure that keeps the pairs connected in metaphase i. Mono-orientation of sister kinetochores and segregation of pairs of sister chromatids characterize the completion of meiosis i, while the reductional division of meiosis ii is similar to a mitotic division. Considering this astounding complexity, it is not surprising that meiocytes contain more than one type of cohesin complex (for cohesin reviews see refs. 1–3). The identification of ReC8 as a meiosis-specific kleisin, i.e., a protein that closes the cohesin ring, followed by the description of the meiosis-specific sCC3-like sA3 (sTAG3) protein and of a variant of the sMC1 protein called sMC1b, revealed a high variety among cohesin complexes. Most recently, three groups described yet another meiosis-specific cohesin subunit: RAD21L. Data mining by the groups of yoshinori watanabe, 4 Tatsuya Hirano 5 and, as reported in the May 1st issue of Cell Cycle , the group of Alberto Pendas led to the identification of this kleisin, which is expressed in spermatocytes and oocytes. RAD21L localizes to emerging Aes at the entry into meiosis. Upon synapsis, RAD21L remains sC-associated until it gradually disappears towards the end of pachytene, at least on autosomes, even though the sC is still intact. This disappearance correlates with the dissolution of MsH4 foci and the appearance of MLH1 foci, indicators of sites of crossoves and chiasmata. ishiguro et al. reported that in meta-phase i spermatocytes, RAD21L is restricted to the centromere, while in metaphase i oocytes, RAD21L is not detectable. staining beyond pachytene was not seen by Lee and Hirano and not reported by Guiterrez-Caballero et al. The staining pattern is roughly similar to that of ReC8 but differs in important detail. ReC8 may appear a bit later in leptotene, although several studies differ in this respect, and RAD21L may be involved in synapsis initiation. The two proteins localize in a mutually exclusive manner along pachytene chromosomes, as if RAD21L would support the chromosomal loop-axis structure at some locations and ReC8 at others. RAD21 rarely colocalizes with RAD21L or ReC8. interestingly, the Hirano and watanabe groups suggest loading of RAD21 complex(es) onto late …