DNA strand resection involved in replication fork processing
Definition
Target type: biologicalprocess
The 5' to 3' exonucleolytic resection of DNA at the site of a stalled replication fork that contributes to replication fork processing. [GOC:mah, PMID:28475874]
DNA strand resection is a crucial step in the processing of replication forks, which are the sites where DNA replication occurs. During DNA replication, the two strands of the DNA double helix are unwound and separated, creating a replication fork. At this fork, the leading strand is continuously synthesized, while the lagging strand is synthesized discontinuously in short fragments called Okazaki fragments. Strand resection is the process of removing nucleotides from the 5' end of the lagging strand and from the 5' end of a broken DNA strand. This process is essential for preparing the DNA for repair and for priming the lagging strand for DNA synthesis.
The process of strand resection is initiated by the MRN complex (Mre11, Rad50, and Nbs1) which binds to the DNA double-strand break (DSB). The MRN complex recruits the nuclease CtIP, which initiates 5'-3' resection. CtIP works with the MRN complex to remove short stretches of nucleotides.
Once the process is initiated, two key enzymes, EXO1 and DNA2, take over and perform the majority of the resection. EXO1 is a 5'-3' exonuclease, meaning it removes nucleotides from the 5' end of a DNA strand, while DNA2 is a 5'-3' exonuclease and helicase, meaning it can unwind the DNA double helix and remove nucleotides. These enzymes work together to extend the 3' single-stranded tail, which is required for the initiation of lagging strand synthesis.
The 3' single-stranded tail is then coated with a protein called Replication Protein A (RPA), which stabilizes the single-stranded DNA and prevents it from re-annealing with the complementary strand. RPA also serves as a platform for other proteins involved in DNA repair and replication.
Strand resection is a highly regulated process that is essential for maintaining the integrity of the genome. It is tightly controlled by a variety of factors, including the cell cycle, the presence of DNA damage, and the availability of DNA repair factors. Errors in strand resection can lead to mutations and genomic instability, which can contribute to the development of cancer and other diseases. '
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| BRCA1-associated RING domain protein 1 | A BRCA1-associated RING domain protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99728] | Homo sapiens (human) |
| Breast cancer type 1 susceptibility protein | A breast cancer type 1 susceptibility protein that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Compounds (1)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| beta-thujaplicin | beta-thujaplicin : A monoterpenoid that is cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. Isolated from Thuja plicata and Chamaecyparis obtusa, it exhibits antimicrobial activities. beta-thujaplicin: structure | cyclic ketone; enol; monoterpenoid | antibacterial agent; antifungal agent; antineoplastic agent; antiplasmodial drug; plant metabolite |