Role of the Checkpoint Clamp in DNA Damage Response
نویسنده
چکیده
DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen)-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR).
منابع مشابه
The Role of chk2 in Response to DNA Damage in Cancer Cells
Accumulation of gene changes and chromosomal instability in response to cellular DNA damage lead to cancer. DNA damage induces cell cycle checkpoints pathways. Checkpoints regulate DNA replication and cell cycle progression, chromatin restructuring, and apoptosis. Checkpoint kinase 2 (chk2) is activated in response to DNA lesions. ATM phosphorylate chk2. The activated Chk2 kinase can phosphoryl...
متن کاملPap1+ confers microtubule damage resistance to mut2a, an extragenic suppressor of the rad26:4A allele in S. pombe.
The DNA structure checkpoint protein Rad26ATRIP is also required for an interphase microtubule damage response. This checkpoint delays spindle pole body separation and entry into mitosis following treatment of cells with microtubule poisons. This checkpoint requires cytoplasmic Rad26ATRIP, which is compromised by the rad26:4A allele that inhibits cytoplasmic accum...
متن کاملPurification and characterization of human DNA damage checkpoint Rad complexes.
Checkpoint Rad proteins function early in the DNA damage checkpoint signaling cascade to arrest cell cycle progression in response to DNA damage. This checkpoint ensures the transmission of an intact genetic complement to daughter cells. To learn about the damage sensor function of the human checkpoint Rad proteins, we purified a heteropentameric complex composed of hRad17-RFCp36-RFCp37-RFCp38-...
متن کاملDrug-sensitive DNA polymerase δ reveals a role for mismatch repair in checkpoint activation in yeast.
We have used a novel method to activate the DNA damage S-phase checkpoint response in Saccharomyces cerevisiae to slow lagging-strand DNA replication by exposing cells expressing a drug-sensitive DNA polymerase δ (L612M-DNA pol δ) to the inhibitory drug phosphonoacetic acid (PAA). PAA-treated pol3-L612M cells arrest as large-budded cells with a single nucleus in the bud neck. This arrest requir...
متن کاملThe 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1
Single-stranded DNA (ssDNA) at DNA ends is an important regulator of the DNA damage response. Resection, the generation of ssDNA, affects DNA damage checkpoint activation, DNA repair pathway choice, ssDNA-associated mutation and replication fork stability. In eukaryotes, extensive DNA resection requires the nuclease Exo1 and nuclease/helicase pair: Dna2 and Sgs1(BLM). How Exo1 and Dna2-Sgs1(BLM...
متن کامل