Publications by authors named "Alina Vaitsiankova"

Article Synopsis
  • PARP inhibitors (PARPi) show promise in cancer treatment but have been linked to severe anemia and leukemia, complicating their use.
  • Research indicates that mice with inactive PARP2 face severe blood production issues, suggesting a critical role of PARP2 in erythropoiesis (red blood cell formation) during development.
  • Active PARP2 is essential for DNA replication and repair, particularly at specific DNA damage sites; its inactivity leads to harmful effects in blood cell production, providing insights into the anemia seen with PARPi treatment.
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Article Synopsis
  • Mammalian DNA replication requires various helicases and nucleases for accurate genetic duplication, but the direction of these activities was previously unclear.
  • The study identifies USP50 as a crucial chromatin-associated protein that aids in ongoing replication, fork restart, and telomere maintenance, while also preventing DNA breaks.
  • USP50 works by ensuring the correct localization of other proteins like WRN and FEN1 during stalled replication, and its absence leads to increased activity of certain helicases and nucleases, causing replication issues and telomere instability.
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Unlabelled: PARP1&2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to enzymatic inhibition, PARPi also trap PARP1&2 at DNA lesions.

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Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses.

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Mammalian DNA replication employs several RecQ DNA helicases to orchestrate the faithful duplication of genetic information. Helicase function is often coupled to the activity of specific nucleases, but how helicase and nuclease activities are co-directed is unclear. Here we identify the inactive ubiquitin-specific protease, USP50, as a ubiquitin-binding and chromatin-associated protein required for ongoing replication, fork restart, telomere maintenance and cellular survival during replicative stress.

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In a recent issue of , Martin-Rufino et al. develop a strategy for performing high-throughput base-editing CRISPR screens coupled with single-cell readouts in the context of human hematopoiesis. Through a series of proof-of-principle experiments, the authors demonstrate the potential of base-editing screens for the study and treatment of hematological disorders.

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Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments and other DNA replication intermediates, highlighting such structures as potential sources of genome breakage induced by PARP inhibition. Here, we show that PARP1 activity is greatly elevated in chicken and human S phase cells in which FEN1 nuclease is genetically deleted and is highest behind DNA replication forks. PARP inhibitor reduces the integrity of nascent DNA strands in both wild-type chicken and human cells during DNA replication, and does so in FEN1 cells to an even greater extent that can be detected as postreplicative single-strand nicks or gaps.

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The t(8;21) translocation is the most widespread genetic defect found in human acute myeloid leukemia. This translocation results in the RUNX1-RUNX1T1 fusion gene that produces a wide variety of alternative transcripts and influences the course of the disease. The rules of combinatorics and splicing of exons in the RUNX1-RUNX1T1 transcripts are not known.

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