Biology subjects

Shmakova, A.

Publications and source records attributed to Shmakova, A..

3 recordsLinked to original sources

bioRxiv2026

Functional CENP-B boxes are selectively conserved at centromeric regions

Human centromeres are built over large stretches of repetitive, divergent -satellite DNA. Within these sequences lies a conserved, defined 17-bp sequence named the CENP-B box that is bound by the DNA-binding protein CENP-B. Recent studies have proposed that CENP-B box motifs along chromosome arms exist and may represent conserved, ectopic binding sites with functional relevance. Here, we evaluate the genomic distribution, conservation, and binding capacity of different CENP-B box motifs outside canonical centromeres. Analysis of thousands of complete human centromere assemblies reveals exceptional conservation of a unique and canonical CENP-B box motif within centromeres. This is in contrast with the high sequence variability and stochastic occurrence of more degenerate CENP-B box motifs along chromosome arms. Consistently, CENP-B binds only at canonical CENP-B box motifs embedded within -satellite sites, with no evidence of functional binding at any ectopic sites. Together, these results indicate an adaptive selection of canonical CENP-B boxes within centromeric regions, in contrast to random sequence occurrences for ectopic CENP-B box-like motifs.

genomics↗

bioRxiv2024

The Arp2/3 complex maintains genome integrity and survival of epidermal Langerhans cells

Myeloid cells use intracellular actin networks for key cellular processes, including cell migration and chemotaxis, phagocytosis or macropinocytosis, as well as immune synapse formation. However, whether actin networks play any role in the development and/or survival of myeloid cells in tissues remains open. Here, we found that the Arp2/3 complex, which is responsible for the nucleation of branched actin networks, is needed for in vivo maintenance of epidermal Langerhans cells (LCs) throughout life. Mice harboring a genetic deletion of the Arpc4 subunit of the complex in myeloid cells form LC networks at birth, but these cells decline in numbers following a process reminiscent of premature cellular aging. By combining in vivo analyses of LCs with in vitro experiments on bone-marrow-derived dendritic cells, we found that Arpc4-deficient cells manage to progress through the cell cycle but accumulate DNA damage associated with aberrant nuclear shapes, lamina reduction and events of nuclear envelope rupture. These results provide the first evidence for a physiological role of Arp2/3 in maintenance of genome integrity and survival of immune cells in tissues.

cell biology↗

bioRxiv2017

SINHCAF/FAM60A links SIN3A function to the hypoxia response and its levels are predictive of cancer patient survival

The SIN3A-HDAC complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF/FAM60A, links the SIN3A-HDAC co-repressor complex function to the hypoxia response. SINHCAF Chromatin Immunoprecipitation-sequencing and gene expression analysis reveal a signature associated with the activation of the hypoxia response. We show that SINHCAF specifically repress HIF 2 mRNA and protein expression resulting in functional cellular changes in in-vitro angiogenesis, and proliferation. Analysis of patient datasets demonstrates that SINHCAF and HIF 2 mRNA levels are inversely correlated and predict contrasting outcomes for patient survival in both colon and lung cancer. This relationship is also observed in a mouse model of colon cancer, indicating an evolutionary conserved mechanism. Our analysis reveals an unexpected link between SINHCAF and cancer cell signalling via regulation of the hypoxia response that is predictive of poor patient outcome.

molecular biology↗