Abstract
The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this topic has provided novel important clues about nuclear lamina function. These studies have contributed to the knowledge that the lamina constitutes a complex multifunctional platform combining both structural and regulatory functions. Here, we report that, in addition to the previously demonstrated significance for somatic cell differentiation and maintenance, the nuclear lamina is also an essential determinant for germ cell development. Both male and female mice lacking the short meiosis-specific A-type lamin C2 have a severely defective meiosis, which at least in the male results in infertility. Detailed analysis revealed that lamin C2 is required for telomere-driven dynamic repositioning of meiotic chromosomes. Loss of lamin C2 affects precise synapsis of the homologs and interferes with meiotic double-strand break repair. Taken together, our data explain how the nuclear lamina contributes to meiotic chromosome behaviour and accurate genome haploidization on a mechanistic level.
Highlights
Correct segregation of the chromosomes during meiosis depends on accurate prearrangement of the homologs that culminates in their precise and unambiguous pairing
Pairing of homologous chromosomes requires their active repositioning within meiotic nuclei, which depends on the interaction of telomeres with the nuclear envelope
We have investigated the role of the nuclear lamina, a structural scaffold that is intimately associated with the inner nuclear membrane
Summary
Correct segregation of the chromosomes during meiosis depends on accurate prearrangement of the homologs that culminates in their precise and unambiguous pairing. Recent studies established that the nuclear envelope (NE) plays an important role during these processes It functions as a platform for telomere driven chromosome rearrangement, which is essential for chromosome pairing and synapsis [1]. This special role requires a general reorganization of the NE which involves the nuclear lamina, a structural protein network underlying the inner nuclear membrane (INM). As a consequence the structure differs from that typically observed in somatic lamins [8,9] This N-terminal truncation is quite remarkable, as it concerns protein domains, which have been shown to be crucial for the assembly into higher order structures [10,11]. During these movements, attached telomeres are permanently embedded within the lamin C2 enriched
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