Abstract:
:We generated knockout mice for MCM8 and MCM9 and show that deficiency for these genes impairs homologous recombination (HR)-mediated DNA repair during gametogenesis and somatic cells cycles. MCM8(-/-) mice are sterile because spermatocytes are blocked in meiotic prophase I, and females have only arrested primary follicles and frequently develop ovarian tumors. MCM9(-/-) females also are sterile as ovaries are completely devoid of oocytes. In contrast, MCM9(-/-) testes produce spermatozoa, albeit in much reduced quantity. Mcm8(-/-) and Mcm9(-/-) embryonic fibroblasts show growth defects and chromosomal damage and cannot overcome a transient inhibition of replication fork progression. In these cells, chromatin recruitment of HR factors like Rad51 and RPA is impaired and HR strongly reduced. We further demonstrate that MCM8 and MCM9 form a complex and that they coregulate their stability. Our work uncovers essential functions of MCM8 and MCM9 in HR-mediated DSB repair during gametogenesis, replication fork maintenance, and DNA repair.
journal_name
Mol Celljournal_title
Molecular cellauthors
Lutzmann M,Grey C,Traver S,Ganier O,Maya-Mendoza A,Ranisavljevic N,Bernex F,Nishiyama A,Montel N,Gavois E,Forichon L,de Massy B,Méchali Mdoi
10.1016/j.molcel.2012.05.048subject
Has Abstractpub_date
2012-08-24 00:00:00pages
523-34issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(12)00494-7journal_volume
47pub_type
杂志文章相关文献
MOLECULAR CELL文献大全abstract::Trimethylation of histone H3 on lysine 4 (H3K4me3) localizes near the 5' region of genes and is tightly associated with active loci. Several proteins, such as CHD1, BPTF, JMJD2A, and the ING tumor suppressor family, directly recognize this lysine methyl mark. However, how H3K4me3 recognition participates in active tra...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.11.010
更新日期:2007-11-30 00:00:00
abstract::Programmed cell death is a gene-directed process involved in the development and homeostasis of multicellular organisms. The most common mode of programmed cell death is apoptosis, which is characterized by a stereotypical set of biochemical and morphological hallmarks. Here we report that Escherichia coli also exhibi...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.04.027
更新日期:2012-06-08 00:00:00
abstract::How eukaryotic chromosomes fold inside the nucleus is an age-old question that remains unanswered today. Early biochemical and microscopic studies revealed the existence of chromatin domains and loops as a pervasive feature of interphase chromosomes, but the biological implications of such organizational features were...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2016.05.018
更新日期:2016-06-02 00:00:00
abstract::The papillomavirus major late protein, L1, forms the pentameric assembly unit of the viral shell. Recombinant HPV16 L1 pentamers assemble in vitro into capsid-like structures, and truncation of ten N-terminal residues leads to a homogeneous preparation of 12-pentamer, icosahedral particles. X-ray crystallographic anal...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80449-9
更新日期:2000-03-01 00:00:00
abstract::In this issue of Molecular Cell, Weinert et al. (2013) demonstrate that the intermediary metabolite acetyl-phosphate is an important acetyl donor that contributes to global protein acetylation in growth-arrested E. coli. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2013.07.006
更新日期:2013-07-25 00:00:00
abstract::Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophi...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2016.12.025
更新日期:2017-02-02 00:00:00
abstract::The ring-shaped hetero-oligomeric chaperonin TRiC/CCT uses ATP to fold a diverse subset of eukaryotic proteins. To define the basis of TRiC/CCT substrate recognition, we mapped the chaperonin interactions with the VHL tumor suppressor. VHL has two well-defined TRiC binding determinants. Each determinant contacts a spe...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.09.003
更新日期:2006-10-06 00:00:00
abstract::Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2015.04.006
更新日期:2015-06-18 00:00:00
abstract::In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2018.12.013
更新日期:2019-01-03 00:00:00
abstract::HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(00)80056-8
更新日期:1998-03-01 00:00:00
abstract::Cancer cells acquire unlimited proliferative capacity by either re-expressing telomerase or inducing alternative lengthening of telomeres (ALT), which relies on telomere recombination. Here, we show that ALT recombination requires coordinate regulation of the SMX and BTR complexes to ensure the appropriate balance of ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2019.07.010
更新日期:2019-10-03 00:00:00
abstract::The proteolytic activation of the membrane-associated transcription factor pro-sigma(K) is controlled by a signal transduction pathway during sporulation in the bacterium Bacillus subtilis. The pro-sigma(K) processing enzyme SpoIVFB, a membrane-embedded metalloprotease, is held inactive by two other integral-membrane ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2006.05.019
更新日期:2006-07-07 00:00:00
abstract::The nucleotide (p)ppGpp mediates bacterial stress responses, but its targets and underlying mechanisms of action vary among bacterial species and remain incompletely understood. Here, we characterize the molecular interaction between (p)ppGpp and guanylate kinase (GMK), revealing the importance of this interaction in ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2014.12.037
更新日期:2015-02-19 00:00:00
abstract::Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00414-2
更新日期:2001-12-01 00:00:00
abstract::We have analyzed two residues in the helicase domain of the E1 initiator protein. These residues are part of a highly conserved structural motif, the beta-hairpin, which is present in the helicase domain of all papovavirus initiator proteins. These proteins are unique in their ability to transition from local template...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.02.009
更新日期:2007-03-23 00:00:00
abstract::The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s) remain largely unknown. Here, we repo...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2010.08.016
更新日期:2010-09-10 00:00:00
abstract::Tumor cells undergo changes in metabolism to meet their energetic and anabolic needs. It is conceivable that mechanisms exist to sense these changes and link them to pathways that eradicate cells primed for cancer development. We report that the tumor suppressor p53 activates a cell death priming mechanism that senses...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2013.03.016
更新日期:2013-05-09 00:00:00
abstract::Cas4 nucleases are conserved factors in many CRISPR systems, yet their molecular role has remained enigmatic. In this issue of Molecular Cell, Shiimori et al. (2018) report that two Cas4 nucleases together determine the size, orientation, and PAM for foreign DNA snippets acquired by CRISPR loci as immunological memory...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2018.05.028
更新日期:2018-06-07 00:00:00
abstract::Chaperone-mediated autophagy (CMA) is involved in cellular quality control, and in the response to stress, deterioration in CMA contributes to the aging phenotype and to various disorders. The paper by Bandyopadhyay et al. in this issue of Molecular Cell demonstrates the role of GTP binding by elongation factor 1 alph...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2010.08.005
更新日期:2010-08-27 00:00:00
abstract::The proper processing, export, localization, translation, and degradation of mRNAs are necessary for regulation of gene expression. These processes are controlled by mRNA-specific regulatory proteins, noncoding RNAs, and core machineries common to most mRNAs. These factors bind the mRNA in large complexes known as mes...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2014.04.033
更新日期:2014-05-22 00:00:00
abstract::Proliferating metazoan cells respond to damage that has the potential to cause genomic instability by restricting the cell division cycle or by initiating apoptosis. The molecular mechanisms determining the balance between these responses are not well understood. Here, we show that the apoptotic initiator protease cas...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2007.03.019
更新日期:2007-04-27 00:00:00
abstract::The histone methyltransferase PR-Set7/Set8 is the sole enzyme that catalyzes monomethylation of histone H4 at K20 (H4K20me1). Previous reports document disparate evidence regarding PR-Set7 expression during the cell cycle, the biological relevance of PR-Set7 interaction with PCNA, and its role in the cell. We find tha...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2010.10.011
更新日期:2010-11-12 00:00:00
abstract::How polycomb group proteins repress gene expression in vivo is not known. While histone-modifying activities of the polycomb repressive complexes (PRCs) have been studied extensively, in vitro data have suggested a direct activity of the PRC1 complex in compacting chromatin. Here, we investigate higher-order chromatin...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2010.02.032
更新日期:2010-05-14 00:00:00
abstract::Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT ...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.02.003
更新日期:2011-02-18 00:00:00
abstract::The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is composed of three subunits that function together to establish stable kinetochore-microtubule interactions in concert with the Ndc80 network. We show that the structure of the Ska core complex is a W-shaped dime...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2012.03.005
更新日期:2012-05-11 00:00:00
abstract::N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) editing are two of the most abundant RNA modifications, both at adenosines. Yet, the interaction of these two types of adenosine modifications is largely unknown. Here we show a global A-to-I difference between m6A-positive and m6A-negative RNA populations. Bo...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2017.12.006
更新日期:2018-01-04 00:00:00
abstract::Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a majo...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/j.molcel.2011.08.020
更新日期:2011-09-16 00:00:00
abstract::Kong et al. (2020) present the low-resolution structure of the ATPɣS-bound human condensin I and II complexes and demonstrate that human condensins can extrude DNA loops in a symmetric and asymmetric fashion and compact nucleosome-bound DNA. ...
journal_title:Molecular cell
pub_type: 评论,杂志文章
doi:10.1016/j.molcel.2020.06.025
更新日期:2020-07-02 00:00:00
abstract::Polymerase gamma, which replicates and repairs mitochondrial DNA, requires the Pol gamma B subunit for processivity. We determined the crystal structure of mouse Pol gamma B, a core component of the mitochondrial replication machinery. Pol gamma B shows high similarity to glycyl-tRNA synthetase and dimerizes through a...
journal_title:Molecular cell
pub_type: 杂志文章
doi:10.1016/s1097-2765(01)00153-8
更新日期:2001-01-01 00:00:00
abstract::Prions constitute a rare class of protein, which can switch to a robust amyloid form and then propagate that form in the absence of a nucleic acid determinant, thereby creating a unique, protein-only infectious agent. Details of the mechanism that drives conversion to the prion form and then subsequent propagation of ...
journal_title:Molecular cell
pub_type: 杂志文章,评审
doi:10.1016/j.molcel.2004.05.012
更新日期:2004-06-04 00:00:00