Academic Journal

Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSγ Complex for All Crossovers in Mammalian Meiosis

التفاصيل البيبلوغرافية
العنوان: Mutation of the ATPase Domain of MutS Homolog-5 (MSH5) Reveals a Requirement for a Functional MutSγ Complex for All Crossovers in Mammalian Meiosis
المؤلفون: Carolyn R. Milano, J. Kim Holloway, Yongwei Zhang, Bo Jin, Cameron Smith, Aviv Bergman, Winfried Edelmann, Paula E. Cohen
المصدر: G3: Genes, Genomes, Genetics, Vol 9, Iss 6, Pp 1839-1850 (2019)
بيانات النشر: Oxford University Press, 2019.
سنة النشر: 2019
المجموعة: LCC:Genetics
مصطلحات موضوعية: MutS homolog, meiosis, mouse, crossing over, homologous recombination, crossover designation, prophase I, Genetics, QH426-470
الوصف: During meiosis, induction of DNA double strand breaks (DSB) leads to recombination between homologous chromosomes, resulting in crossovers (CO) and non-crossovers (NCO). In the mouse, only 10% of DSBs resolve as COs, mostly through a class I pathway dependent on MutSγ (MSH4/ MSH5) and MutLγ (MLH1/MLH3), the latter representing the ultimate marker of these CO events. A second Class II CO pathway accounts for only a few COs, but is not thought to involve MutSγ/ MutLγ, and is instead dependent on MUS81-EME1. For class I events, loading of MutLγ is thought to be dependent on MutSγ, however MutSγ loads very early in prophase I at a frequency that far exceeds the final number of class I COs. Moreover, loss of MutSγ in mouse results in apoptosis before CO formation, preventing the analysis of its CO function. We generated a mutation in the ATP binding domain of Msh5 (Msh5GA). While this mutation was not expected to affect MutSγ complex formation, MutSγ foci do not accumulate during prophase I. However, most spermatocytes from Msh5GA/GA mice progress to late pachynema and beyond, considerably further than meiosis in Msh5−/− animals. At pachynema, Msh5GA/GA spermatocytes show persistent DSBs, incomplete homolog pairing, and fail to accumulate MutLγ. Unexpectedly, Msh5GA/GA diakinesis-staged spermatocytes have no chiasmata at all from any CO pathway, indicating that a functional MutSγ complex is critical for all CO events regardless of their mechanism of generation.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2160-1836
Relation: https://doaj.org/toc/2160-1836
DOI: 10.1534/g3.119.400074
URL الوصول: https://doaj.org/article/6dabb039d2a94199956e7866f013d0b3
رقم الانضمام: edsdoj.6dabb039d2a94199956e7866f013d0b3
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:21601836
DOI:10.1534/g3.119.400074