BRCA2 and Genome Integrity

In a previous report, we found that mutations at the mitochondrial genome integrity locus, MGI1, can convert Kluyveromyces lactis into a petite-positive yeast. In this report, we describe the isolation of the MGI1 gene and show that it encodes the β-subunit of the mitochondrial F1-ATPase. The site of mutation in four independently isolated mgi1 alleles is at Arg435, which has changed to Gly in three cases and Ile in the fourth isolate. Disruption of MGI1 does not lead to the production of mitochondrial genome deletion mutants, indicating that an assembled F1 complex is needed for the “gain-of-function” phenotype found in mgi1 point mutants. The location of Arg435 in the β-subunit, as deduced from the three-dimensional structure of the bovine F1-ATPase, together with mutational sites in the previously identified mgi2 and mgi5 alleles, suggests that interaction of the β- and α- (MGI2) subunits with the γ-subunit (MGI5) is likely to be affected by the mutations.

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A matter of wrapper: Defects in the nuclear envelope of lagging and bridging chromatin threatens genome integrity

Seminars in Cell and Developmental Biology ◽

10.1016/j.semcdb.2021.03.004 ◽

2021 ◽

Author(s):

Marina Rodriguez-Muñoz ◽

Teresa Anglada ◽

Anna Genescà

Keyword(s):

Nuclear Envelope ◽

Genome Integrity

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A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity

Cancers ◽

10.3390/cancers13071583 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1583

Author(s):

Sara Pescatori ◽

Francesco Berardinelli ◽

Jacopo Albanesi ◽

Paolo Ascenzi ◽

Maria Marino ◽

...

Keyword(s):

Dna Damage ◽

Cellular Transformation ◽

Genome Integrity ◽

Physiological Effects ◽

Dna Damages ◽

Cellular Effects ◽

Damage Response ◽

17Β Estradiol ◽

Cellular Pathways ◽

Definition Of

17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects.

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USP15 Deubiquitinase Safeguards Hematopoiesis and Genome Integrity in Hematopoietic Stem Cells and Leukemia Cells

Cell Reports ◽

10.1016/j.celrep.2020.108533 ◽

2020 ◽

Vol 33 (13) ◽

pp. 108533

Author(s):

Paul van den Berk ◽

Cesare Lancini ◽

Carlos Company ◽

Michela Serresi ◽

Maria Pilar Sanchez-Bailon ◽

...

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Leukemia Cells ◽

Genome Integrity ◽

Hematopoietic Stem

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