Target type: biologicalprocess
Any DNA biosynthetic process that is involved in mitotic DNA replication. [GO_REF:0000060, GOC:TermGenie, PMID:16849602]
DNA synthesis during mitotic replication is a complex and highly regulated process that ensures the faithful duplication of the entire genome before cell division. The process can be broken down into several key steps:
1. **Origin Recognition and Licensing:** Replication begins at specific sites on the DNA molecule called origins of replication. These origins are recognized and bound by a complex of proteins known as the origin recognition complex (ORC). ORC marks the origin as a potential site for initiation, but the actual initiation event requires the activity of other proteins.
2. **Pre-Replication Complex (pre-RC) Formation:** Once ORC is bound, other proteins such as Cdc6 and Cdt1 join the complex, forming the pre-RC. This complex is crucial for initiating replication, but it can only form during a specific phase of the cell cycle (G1 phase), ensuring that DNA is replicated only once per cell cycle.
3. **Initiation:** At the beginning of S phase, a protein kinase called cyclin-dependent kinase (CDK) becomes active, phosphorylating components of the pre-RC. This phosphorylation activates the DNA helicase, a protein complex composed of MCM2-7 proteins, which unwinds the double helix of DNA, separating the two strands.
4. **Primer Synthesis:** A short RNA primer is synthesized by DNA primase, providing a starting point for DNA polymerase.
5. **Elongation:** DNA polymerase enzymes, specifically DNA polymerase α, δ, and ε, synthesize new DNA strands using the parental strands as templates. These polymerases work in a 5' to 3' direction, adding nucleotides one at a time to the 3' end of the growing strand.
6. **Leading and Lagging Strand Synthesis:** Since DNA polymerase can only synthesize DNA in the 5' to 3' direction, one strand (the leading strand) is synthesized continuously towards the replication fork. The other strand (the lagging strand) is synthesized discontinuously in short fragments called Okazaki fragments, which are later joined together by DNA ligase.
7. **Termination:** Eventually, replication forks from adjacent origins collide, leading to the termination of DNA synthesis.
8. **Proofreading:** DNA polymerases have a proofreading function, removing mismatched nucleotides and maintaining the accuracy of DNA replication.
9. **Chromatin Assembly:** As new DNA strands are synthesized, histones associate with the newly synthesized DNA to re-establish the nucleosomes, the basic units of chromatin structure.
This intricate process ensures the accurate and complete duplication of the entire genome, allowing for the faithful transmission of genetic information from one generation of cells to the next.'
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Protein | Definition | Taxonomy |
---|---|---|
Thymidine kinase, cytosolic | A thymidine kinase, cytosolic that is encoded in the genome of human. [PRO:DNx, UniProtKB:P04183] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
thymidine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; metabolite; mouse metabolite | |
idoxuridine | organoiodine compound; pyrimidine 2'-deoxyribonucleoside | antiviral drug; DNA synthesis inhibitor | |
bromodeoxyuridine | Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. | pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent |
cytarabine | beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside | antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent | |
thymidine monophosphate | dTMP : The neutral species of thymidine 5'-monophosphate (2'-deoxythymidine 5'-monophosphate). Thymidine Monophosphate: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety. | thymidine 5'-monophosphate | fundamental metabolite |
deoxyuridine | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
2'-deoxyadenosine | 2'-deoxyformycin A: RN not in Chemline 9/85; RN and structure given in first source | purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
stavudine | stavudine : A nucleoside analogue obtained by formal dehydration across positions 2 and 3 of thymidine. An inhibitor of HIV-1 reverse transcriptase Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV. | dihydrofuran; nucleoside analogue; organic molecular entity | antimetabolite; antiviral agent; EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor |
vidarabine | adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. | beta-D-arabinoside; purine nucleoside | antineoplastic agent; bacterial metabolite; nucleoside antibiotic |
zidovudine | zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase. Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. | azide; pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
fialuridine | |||
thymine arabinoside | thymine arabinoside: selectively inhibits replication of herpes simplex virus | N-glycosyl compound | |
2',3'-didehydro-2',3'-dideoxyuridine | |||
3'-azido-3'-deoxythymidine 5'phosphate | 3'-azido-3'-deoxythymidine 5'phosphate: inhibits thymidylate kinase | ||
clevudine | |||
5-propyl-2'-deoxyuridine | 5-propyl-2'-deoxyuridine: RN given refers to parent cpd | ||
5'-o-dimethyltritylthymidine | |||
1-(2-deoxy-2-fluoroarabinofuranosyl)-5-ethyluracil | 1-(2-deoxy-2-fluoroarabinofuranosyl)-5-ethyluracil: RN given refers to (beta-D)-isomer; structure given in first source | ||
(north)-methanocarbathymidine | (north)-methanocarbathymidine: also called NMCT 1-[(1S,2S,4S,5R)-4-hydroxy-5-(hydroxymethyl)bicyclo[3.1.0]hexan-2-yl]thymine : A carbobicyclic compound that is bicyclo[3.1.0]hexane which is substituted at the 2-pro-S, 4-pro-S and 5-pro-R positions by thymin-1-yl, hydroxy, and hydroxymethyl groups, respectively. | C-glycosyl pyrimidine; carbobicyclic compound; primary alcohol; pyrimidone; secondary alcohol | |
brivudine | brivudine: anti-herpes agent | ||
carbocyclic 5-iodo-2'-deoxyuridine | |||
2',3'-didehydro-3'-deoxy-4'-ethynylthymidine | 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine: a highly active anti-HIV agent; structure in first source | ||
deoxy-4-thiothymidine | 4-thiothymidine: structure in first source | ||
sorivudine | organic molecular entity | ||
acyclovir | acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections. Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. | 2-aminopurines; oxopurine | antimetabolite; antiviral drug |
deoxyguanosine | purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite | |
9-(4-hydroxybutyl)guanine | |||
9-arabinofuranosylguanine | 9-arabinofuranosylguanine: RN given refers to (beta)-isomer 9-beta-D-arabinofuranosylguanine : A purine nucleoside in which guanine is attached to arabinofuranose via a beta-N(9)-glycosidic bond. It inhibits DNA synthesis and causes cell death. | beta-D-arabinoside; purine nucleoside | antineoplastic agent; DNA synthesis inhibitor |