Distinct Roles of Meiosis-Specific Cohesin Complexes in Mammalian Spermatogenesis

被引:56
作者
Biswas, Uddipta [1 ]
Hempel, Kai [1 ]
Llano, Elena [2 ]
Pendas, Alberto [2 ]
Jessberger, Rolf [1 ]
机构
[1] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Physiol Chem, Dresden, Germany
[2] USAL, CSIC, Ctr Invest Canc, Campus Miguel de Unamuno, Salamanca, Spain
关键词
CHROMOSOME DYNAMICS; STAG3; REC8; TELOMERES; SMC1-BETA; SYNAPSIS; RAD21L; DNA;
D O I
10.1371/journal.pgen.1006389
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mammalian meiocytes feature four meiosis-specific cohesin proteins in addition to ubiquitous ones, but the roles of the individual cohesin complexes are incompletely understood. To decipher the functions of the two meiosis-specific kleisins, REC8 or RAD21L, together with the only meiosis-specific SMC protein SMC1 beta, we generated Smc1 beta(-/-) Rec8(-/-) and Smc1 beta(-/-) Rad21L(-/-) mouse mutants. Analysis of spermatocyte chromosomes revealed that besides SMC1 beta complexes, SMC1 alpha/RAD21 and to a small extent SMC1 alpha/REC8 contribute to chromosome axis length. Removal of SMC1 beta and RAD21L almost completely abolishes all chromosome axes. The sex chromosomes do not pair in single or double mutants, and autosomal synapsis is impaired in all mutants. Super resolution microscopy revealed synapsis-associated SYCP1 aberrantly deposited between sister chromatids and on single chromatids in Smc1 beta(-/-) Rad21L(-/-) cells. All mutants show telomere length reduction and structural disruptions, while wild-type telomeres feature a circular TRF2 structure reminiscent of t-loops. There is no loss of centromeric cohesion in both double mutants at leptonema/early zygonema, indicating that, at least in the mutant backgrounds, an SMC1 alpha/RAD21 complex provides centromeric cohesion at this early stage. Thus, in early prophase I the most prominent roles of the meiosis-specific cohesins are in axis-related features such as axis length, synapsis and telomere integrity rather than centromeric cohesion.
引用
收藏
页数:24
相关论文
共 32 条
[1]   Cohesin SMC1β protects telomeres in meiocytes [J].
Adelfalk, Caroline ;
Janschek, Johannes ;
Revenkova, Ekaterina ;
Blei, Cornelia ;
Liebe, Bodo ;
Goeb, Eva ;
Alsheimer, Manfred ;
Benavente, Ricardo ;
de Boer, Esther ;
Novak, Ivana ;
Hoog, Christer ;
Scherthan, Harry ;
Jessberger, Rolf .
JOURNAL OF CELL BIOLOGY, 2009, 187 (02) :185-199
[2]   Positional cloning and characterization of mouse mei8, a disrupted allele of the meiotic cohesin Rec8 [J].
Bannister, LA ;
Reinholdt, LG ;
Munroe, RJ ;
Schimenti, JC .
GENESIS, 2004, 40 (03) :184-194
[3]  
BISWAS U, 2013, PLOS GENET, V9, DOI DOI 10.1371/J0URNAL.PGEN.1003985
[4]   Spermatogonial stem cells [J].
de Rooij, DG ;
Grootegoed, JA .
CURRENT OPINION IN CELL BIOLOGY, 1998, 10 (06) :694-701
[5]   Super-Resolution Fluorescence Imaging of Telomeres Reveals TRF2-Dependent T-loop Formation [J].
Doksani, Ylli ;
Wu, John Y. ;
de Lange, Titia ;
Zhuang, Xiaowei .
CELL, 2013, 155 (02) :345-356
[6]   Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1β and SMC3 [J].
Eijpe, M ;
Offenberg, H ;
Jessberger, R ;
Revenkova, E ;
Heyting, C .
JOURNAL OF CELL BIOLOGY, 2003, 160 (05) :657-670
[7]   STAG3-mediated stabilization of REC8 cohesin complexes promotes chromosome synapsis during meiosis [J].
Fukuda, Tomoyuki ;
Fukuda, Nanaho ;
Agostinho, Ana ;
Hernandez-Hernandez, Abrahan ;
Kouznetsova, Anna ;
Hoog, Christer .
EMBO JOURNAL, 2014, 33 (11) :1243-1255
[8]   Mammalian telomeres end in a large duplex loop [J].
Griffith, JD ;
Comeau, L ;
Rosenfield, S ;
Stansel, RM ;
Bianchi, A ;
Moss, H ;
de Lange, T .
CELL, 1999, 97 (04) :503-514
[9]   Identification and molecular characterization of the mammalian α-kleisin RAD21L [J].
Gutierrez-Caballero, Cristina ;
Herran, Yurema ;
Sanchez-Martin, Manuel ;
Angel Suja, Jose ;
Luis Barbero, Jose ;
Llano, Elena ;
Pendas, Alberto M. .
CELL CYCLE, 2011, 10 (09) :1477-1487
[10]   The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility [J].
Herran, Yurema ;
Gutierrez-Caballero, Cristina ;
Sanchez-Martin, Manuel ;
Hernandez, Teresa ;
Viera, Alberto ;
Luis Barbero, Jose ;
de Alava, Enrique ;
de Rooij, Dirk G. ;
Angel Suja, Jose ;
Llano, Elena ;
Pendas, Alberto M. .
EMBO JOURNAL, 2011, 30 (15) :3091-3105