Table of Contents
What is base and nucleotide excision repair?
Base excision repair (BER) and nucleotide excision repair (NER) are two DNA-repair pathways that, like other DNA-repair pathways except for direct reversal of DNA damage, involve sequential activities of multiple repair proteins.
What is the role of TFIIH in the transcription complex?
TFIIH is a multifunctional complex composed of 10 subunits, with an essential role in transcription, in which it functions in promoter opening, RNA polymerase II (RNAPII) phosphorylation, and promoter escape; this along with a central role in NER by promoting damaged strand discrimination, DNA opening, and endonuclease …
What is nucleotide excision repair in DNA?
Nucleotide excision repair (NER) is the main pathway used by mammals to remove bulky DNA lesions such as those formed by UV light, environmental mutagens, and some cancer chemotherapeutic adducts from DNA. Deficiencies in NER are associated with the extremely skin cancer-prone inherited disorder xeroderma pigmentosum.
How does base excision repair work?
Base excision repair (BER) corrects small base lesions that do not significantly distort the DNA helix structure. It is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site which is further processed by short-patch repair or long-patch repair.
What does base excision repair fix?
DNA damage
Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure.
Why is TFIIH important?
The TFIIH subunit XPB is arguably the most important for pol II transcription, as it contains an ATPase and translocase activity that enables ATP‐dependent opening of the promoter DNA at the transcription start site.
How does TFIIH initiate transcription?
During transcription of protein coding genes, the ATP-dependent helicase activity of XPB is required for promoter opening, and the cyclin-dependent kinase 7 (CDK7) kinase subunit of TFIIH promotes the phosphorylation of RNA polymerase II to initiate transcription.
What happens during nucleotide excision repair?
In nucleotide excision repair (NER), damaged bases are cut out within a string of nucleotides, and replaced with DNA as directed by the undamaged template strand. This repair system is used to remove pyrimidine dimers formed by UV radiation as well as nucleotides modified by bulky chemical adducts.
What type of DNA is repaired by base excision repair?
Base Excision Repair of DNA Damage BER involves the excision of a single base rather than the nucleotide and is most commonly used to repair damage caused by endogenous DNA insult and is especially important for cellular response to oxidative DNA damage.
What does nucleotide repair do?
What is the meaning of TFIIH?
Transcription factor IIH (TFIIH) is a heterodecameric protein complex critical for transcription initiation by RNA polymerase II and nucleotide excision DNA repair.
Is Tfiih a kinase?
The TFIIH‐associated kinase CDK7 (Kin28 in S. cerevisiae) influences pol II transcription beyond the promoter‐proximal region, via phosphorylation of the pol II CTD.
What does base excision repair?
Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure.
Does TFIIH bind to TATA box?
TFIIA binds to the TBP and interacts with a site within the TATA box region (1). This protein factor serves to stabilize the interactions between the DNA and the TBP. TFIIA also binds activators and displaces repressors, which is necessary for transcriptional activation.
What is the difference between TATA box and CAAT box?
TATA box is a conserved nucleotide region found about 25-30 base pairs upstream to the transcription initiation site. On the other hand, CAAT box is a conserved region of nucleotides found about 75-80 base pairs upstream to the transcription initiation site. So, this is the key difference between TATA and CAAT box.
What is nucleotide excision repair?
Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents ), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleotide excision repair (NER), base excision repair (BER), and DNA mismatch repair (MMR).
What is the structure of the NER intermediate around TFIIH?
Nucleotide excision repair (NER) is the major DNA repair pathway that removes UV-induced and bulky DNA lesions. There is currently no structure of NER intermediates, which form around the large multisubunit transcription factor IIH (TFIIH). Here we report the cryo-EM structure of an NER intermediate containing TFIIH and the NER factor XPA.
How does TFIIH orchestrate DNA duplex opening and damage verification?
“XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase”. DNA Repair (Amst.). 10 (7): 697–713. doi: 10.1016/j.dnarep.2011.04.028. PMC 3234290. PMID 21571596.
How is DNA damaged removed from the cell membrane?
In both prokaryotes and eukaryotes, a major cellular mechanism for the removal of DNA damage is nucleotide excision repair (excision repair), an enzymatic pathway that recognizes and corrects a wide spectrum of structural anomalies (DNA lesions) ranging from bulky, helix-distorting adducts to nonhelix-distorting lesions.