Representative images of selected DNA repair and checkpoint proteins Biology Diagrams The repair of DNA lesions that occur endogenously or in response to diverse genotoxic stresses is indispensable for genome integrity. DNA lesions activate checkpoint pathways that regulate The integrity of genomic DNA is continually monitored and DNA repair is coordinated with the cell cycle via the G1/S, intra-S phase, and G2/M checkpoints. During mitosis, communication between the mitotic checkpoint complex (MCC) and anaphase-promoting complex/cyclosome (APC/C) ensures the proper alignment and segregation of chromosomes. The signal transducers activate p53 and inactivate cyclin-dependent kinases to inhibit cell cycle progression from G1 to S (the G1/S checkpoint), DNA replication (the intra-S checkpoint), or G2 to mitosis (the G2/M checkpoint). In this review the molecular mechanisms of DNA repair and the DNA damage checkpoints in mammalian cells are analyzed.
Keywords: Checkpoint, DNA damage, Cell cycle, Genome stability, Mitosis. While there are many lesion-specific responses for DNA repair, different lesions in genomic DNA activate common checkpoint pathways whose goal is to maintain CDKs in an inactive state until the lesion is removed. Broadly speaking, DNA damage checkpoints can be
Regulation of DNA repair throughout the cell cycle Biology Diagrams
In sum, apical kinases perform highly elaborate actions in the spatiotemporal control of checkpoint responses and DNA repair. Since checkpoint functions and early resection blockades can counteract HRโmediated DNA repair mechanisms, the ability of cells to modulate DNA damage signaling is essential for repair pathway control, and, in
A recent study used immunofluorescence (IF) staining of repair proteins as surrogate markers to examine DSBs, SSBs, and base damages in human cells to directly visualize the induction and repair of clustered DNA lesions at the single-cell level . Results showed that a large fraction of 53BP1, XRCC1, and hOGG1 foci colocalized with another
Cell Cycle Regulation by Checkpoints Biology Diagrams
From bacteria to mammalian cells, damaged DNA is sensed and targeted by DNA repair pathways. In eukaryotes, kinases play a central role in coordinating the DNA damage response. DNA damage signaling kinases were identified over two decades ago and linked to the cell cycle checkpoint concept proposed by Weinert and Hartwell in 1988.
