Publications by authors named "S M Waga"

Introduction: The concurrent occurrence of infectious diseases (IDs) and non-communicable diseases (NCDs) presents complex healthcare challenges in sub-Saharan Africa (SSA), where healthcare systems often grapple with limited resources. While an integrated care approach has been advocated to address these complex challenges, there is a recognised gap in comprehensive evidence regarding the various models of integrated care, their components and the feasibility of their implementation. This scoping review aims to bridge this gap by examining the breadth and nature of evidence on integrated care models for NCDs and IDs within SSA, thereby updating the current evidence base in the domain.

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Human origin recognition complex (hORC) binds to the DNA replication origin and then initiates DNA replication. However, hORC does not exhibit DNA sequence-specificity and how hORC recognizes the replication origin on genomic DNA remains elusive. Previously, we found that hORC recognizes G-quadruplex structures potentially formed near the replication origin.

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Cells must coordinate the activation of thousands of replication origins dispersed throughout their genome. Active transcription is known to favor the formation of mammalian origins, although the role that RNA plays in this process remains unclear. We show that the ORC1 subunit of the human Origin Recognition Complex interacts with RNAs transcribed from genes with origins in their transcription start sites (TSSs), displaying a positive correlation between RNA binding and origin activity.

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Article Synopsis
  • - The Origin Recognition Complex (ORC) is crucial for DNA replication in eukaryotes, but how it identifies replication origins in humans is not well understood.
  • - Research indicates that human ORC subunit 1 (hORC1) shows a strong preference for G-rich DNA sequences that can form G-quadruplex (G4) structures, particularly in promoter and telomere areas.
  • - Studies using fluorescence anisotropy and other techniques confirmed that hORC1 binds specifically to G4 structures, maintaining their formation even after binding, suggesting that G4 structures play a key role in how human ORC recognizes replication origins.
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DNA interstrand cross-links (ICLs) are repaired in S phase by a complex, multistep mechanism involving translesion DNA polymerases. After replication forks collide with an ICL, the leading strand approaches to within one nucleotide of the ICL ("approach"), a nucleotide is inserted across from the unhooked lesion ("insertion"), and the leading strand is extended beyond the lesion ("extension"). How DNA polymerases bypass the ICL is incompletely understood.

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