Exam 02 DNa Replication/Repair Flashcards
What is chromatin
-protein + nuclear DNA
Heterochromatin
- very condensed (stains darkly throughout cell cycle even interphase)
- late replicating and genetically inactive
- highly concentrated at centromeres and telomeres
- contain very few genes
- genes will be silenced if relocated near Heterochromatin
Euchromatin is less condensed
Interactions between DNA and histone
- H+ bond formed with DNA and histone core in each nucleosome
- hydrophobic interactions
- salt linkages= Lys and Arg to neutralize negative charge of DNA backbone
Direct Repair
Enzymatic Repair
- types of damage repaired
- pyrimidine dimers
- O6-methylguanine
- enzyme/mechanism
- DNA photolyase
- methylguanine methyltransferase
Base Excision Repair (BER)
*Type of damage repaired
-single-base mismatches, nondistorting alterations
Ex) depurination
- ENzymes/mechanism
- DNA glycolases, AP endonuclease, AP lyase, DNA polymerase, DNA ligase
Nucleotide Excision Repair (NER)
*types of damage repaired:
-chemical adducts that distort DNA
Ex) pyrimidine dimers, BPDE-guanine adducts, cisplatin adducts
- enzymes/mechanism:
- NER protein complex, DNA polymerase, DNA ligase
- disease:
- Xeroderma pigmentosum
Mismatch Excision Repair (MER)
- type of damage repaired:
- mismatched base in daughter strand
- enzyme/mechanism:
- MER complex, helicase/endonuclease, DNA pol, DNA ligase
- disorder:
- hereditary nonpolyposis
- colorectal cancers
Recombination Repair
NON-homologous end joining (NHE)
- type of damage repaired:
- double stranded breaks, interstrand crosslinking
- enzyme/mechanism:
- damaged ends filled in and joined, some base pairs may be missing
- multiple proteins and enzymes including DNA ligase
Recombination Repair
Homologous recombination
- types of damage repaired:
- double strand breaks, interstrand crosslinking
- enzyme/Mechanism:
- exonuclease, DNA pol, MER system, damages duplex repair using info on undamaged homologous duplex
- disorder:
- BRCA1/2 breast cancer
Transcription coupled repair (TCR)
- types of damage repaired:
- stalled RNA pol during transcription (NOT replication)
- disorders:
- Cockayne syndrome
Helicase
Unwinds DNA
-hydrolyzes ATP (confromation change propels it along ssDNA)
Topoisomerase
- relieves overwound supercoils (called DNA gyrase in bacteria)
- as replication fork moves it creates winding problem for parental helix
- reversible enzyme that breaks a phosphodiester bond to change superhelicity thereby relieving supercoiling
Single stranded DNA binding protein (ssDNA)
- binds ssDNA that has been separated (exposed)
- helps stabilize unwound DNA (prevents hairpin loop)
- keeps DNA exposed for easy access for DNA pol
DNA polymerase
- only synthesize in 5’–>3’ direction so there is leading and lagging strand
- adds nucleotides (release PiPi)
- requires primer with 3’OH end to begin
- has proofreading (tightens fingers at active site to see if base fits and exonuclease activity)
DNA ligase
-seals nicks