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Calmodulin, a small, ubiquitous Ca 2+ -binding protein, regulates a wide variety of proteins and processes in all eukaryotes. CMD1 , the single gene encoding calmodulin in S. cerevisiae , is essential, and this review discusses studies that identified many of calmodulin's physiological targets and their functions in yeast cells. Calmodulin performs essential roles in mitosis, through its regulation of Nuf1p/Spc110p, a component of the spindle pole body, and in bud growth, by binding Myo2p, an unconventional class V myosin required for polarized secretion. Surprisingly, mutant calmodulins that fail to bind Ca 2+ can perform these essential functions. Calmodulin is also required for endocytosis in yeast and participates in Ca 2+ -dependent, stress-activated signaling pathways through its regulation of a protein phosphatase, calcineurin, and the protein kinases, Cmk1p and Cmk2p. Thus, calmodulin performs important physiological functions in yeast cells in both its Ca 2+ -bound and Ca 2+ -free form.

Alzheimer's disease (AD) is associated with genetic risk factors and widespread epigenetic alterations. 5‐Hydroxymethylcytosine (5hmC), an oxidized derivative of 5‐methylcytosine (5mC), constitutes up to 20% of 5mC in neuronal DNA and is implicated in aging and neurodegeneration. However, the precise roles of DNA modifications in AD remain unclear, partly due to the lack of accurate detection methods. Here, two orthogonal sequencing methods are introduced: CMD1‐Deaminase sequencing (CD‐seq) and CMD1‐TET bisulfite sequencing (CT‐seq), which enable direct, independent detection of 5mC. When combined with APOBEC‐coupled epigenetic sequencing (ACE‐seq) or TET‐assisted bisulfite sequencing (TAB‐seq) for 5hmC mapping, these techniques provide base‐resolution, subtraction‐free profiling of DNA modifications. Applying them to hippocampal tissue from AD model mice, a significant reduction in 5hmC levels is identified without corresponding changes in 5mC, suggesting that 5hmC functions as an independent epigenetic mark in AD pathogenesis. These findings underscore the importance of precise 5mC/5hmC discrimination and suggest that 5hmC and its regulatory pathways may serve as potential therapeutic targets for AD. This study introduces two orthogonal sequencing methods, CMD1‐Deaminase sequencing (CD‐seq) and CMD1‐TET bisulfite sequencing (CT‐seq), that enable direct, independent detection of 5mC. Using these approaches together with ACE‐seq or TAB‐seq for 5hmC identification, the study reveals a significant reduction in 5hmC, but not 5mC, in the hippocampus of Alzheimer's disease (AD) model mice, supporting a role for 5hmC as an independent epigenetic mark in AD pathogenesis.