| 31. |
- Ganai, Rais Ahmad, et al.
(författare)
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DNA Replication - A Matter of Fidelity
- 2016
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 62:5, s. 745-755
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Forskningsöversikt (refereegranskat)abstract
- The fidelity of DNA replication is determined by many factors, here simplified as the contribution of the DNA polymerase (nucleotide selectivity and proofreading), mismatch repair, a balanced supply of nucleotides, and the condition of the DNA template (both in terms of sequence context and the presence of DNA lesions). This review discusses the contribution and interplay between these factors to the overall fidelity of DNA replication.
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| 32. |
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| 33. |
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| 34. |
- Gaullier, Guillaume, et al.
(författare)
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PARP1 and Sox2 : An Unlikely Team of Pioneers to Conquer the Nucleosome.
- 2017
-
Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 65:4, s. 581-582
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Tidskriftsartikel (refereegranskat)abstract
- In this issue of Molecular Cell, Liu and Kraus (2017) demonstrate that the pioneer transcription factor Sox2 requires PARP1 to bind to a subset of its recognition motifs, which are located within nucleosomes across the genome.
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| 35. |
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| 36. |
- Grönroos, Eva, et al.
(författare)
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Control of Smad7 stability by competition between acetylation and ubiquitination
- 2002
-
Ingår i: Molecular Cell. - 1097-2765 .- 1097-4164. ; 10:3, s. 483-493
-
Tidskriftsartikel (refereegranskat)abstract
- Smad proteins regulate gene expression in response to TGFbeta signaling. Here we present evidence that Smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of Smad7 on two lysine residues in its N terminus. Acetylation or mutation of these lysine residues stabilizes Smad7 and protects it from TGFbeta-induced degradation. Furthermore, we demonstrate that the acetylated residues in Smad7 also are targeted by ubiquitination and that acetylation of these lysine residues prevents subsequent ubiquitination. Specifically, acetylation of Smad7 protects it against ubiquitination and degradation mediated by the ubiquitin ligase Smurf1. Thus, our data suggest that competition between ubiquitination and acetylation of overlapping lysine residues constitutes a novel mechanism to regulate protein stability.
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| 37. |
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| 38. |
- Hangen, Emilie, et al.
(författare)
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Interaction between AIF and CHCHD4 Regulates Respiratory Chain Biogenesis
- 2015
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Ingår i: Molecular cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 58:6, s. 1001-1014
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Tidskriftsartikel (refereegranskat)abstract
- Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that, beyond its apoptotic function, is required for the normal expression of major respiratory chain complexes. Here we identified an AIF-interacting protein, CHCHD4, which is the central component of a redox-sensitive mitochondrial intermembrane space import machinery. Depletion or hypomorphic mutation of AIF caused a downregulation of CHCHD4 protein by diminishing its mitochondrial import. CHCHD4 depletion sufficed to induce a respiratory defect that mimicked that observed in AIF-deficient cells. CHCHD4 levels could be restored in AIF-deficient cells by enforcing its AIF-independent mitochondrial localization. This modified CHCHD4 protein reestablished respiratory function in AIF-deficient cells and enabled AIF-deficient embryoid bodies to undergo cavitation, a process of programmed cell death required for embryonic morphogenesis. These findings explain how AIF contributes to the biogenesis of respiratory chain complexes, and they establish an unexpected link between the vital function of AIF and the propensity of cells to undergo apoptosis.
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| 39. |
- Heckl, Dirk, et al.
(författare)
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Toward whole-transcriptome editing with CRISPR-Cas9
- 2015
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Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 58:4, s. 560-562
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Targeted regulation of gene expression holds huge promise for biomedical research. In a series of recent publications (Gilbert et al., 2014; Konermann et al., 2015; Zalatan et al., 2015), sophisticated, multiplex-compatible transcriptional activator systems based on the CRISPR-Cas9 technology and genome-scale libraries advance the field toward whole-transcriptome control.
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| 40. |
- Hewitt, Graeme, et al.
(författare)
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Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD
- 2021
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Ingår i: Molecular Cell. - : Cell Press. - 1097-2765 .- 1097-4164. ; 81:4, s. 767-783.e11
-
Tidskriftsartikel (refereegranskat)abstract
- Chromatin is a barrier to efficient DNA repair, as it hinders access and processing of certain DNA lesions. ALC1/CHD1L is a nucleosome-remodeling enzyme that responds to DNA damage, but its precise function in DNA repair remains unknown. Here we report that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil misincorporation, which reflects the need to remodel nucleosomes following base excision by DNA glycosylases but prior to handover to APEX1. Using CRISPR screens, we establish that ALC1 loss is synthetic lethal with homologous recombination deficiency (HRD), which we attribute to chromosome instability caused by unrepaired DNA gaps at replication forks. In the absence of ALC1 or APEX1, incomplete processing of BER intermediates results in post-replicative DNA gaps and a critical dependence on HR for repair. Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment existing therapeutic strategies for HRD cancers.
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