Damage Tolerance Function can allow DNA replication to continue despite presence of DNA damage (e.g. thymidine dimer) Process DNA polymerase stalls at dimer sliding clamp releases regular DNA polymerase and binds the one of two translesion polymerases error free recognizes that the dimer is normally a thymidine and the polymerase adds an adenosine opposite and continues replication error prone polymerase adds any base opposite the lesion and continues replication Mismatch Repair Process repairs G/T or A/C pairing sometimes misincorporated due to tautomerization of the nucleotide involves MutS, MutH, MutL enzymes strand specific recognizes which is the new strand because it is unmethylated and the old strand is methylated Deficiency hereditary nonpolyposis colorectal cancer aka Lynch syndrome cause hereditary absence of one copy of enzyme hMLH1 or hMSH2 second copy lost due to somatic mutation known as the two-hit model common to many DNA repair deficiencies presentation microsatellite instability di-, tri-, tetranucleotide repeats that can be amplified constant in number in normal cells diagnostic in Lynch syndrome ↑↑ risk of colorectal cancer NOT preceded by benign polyps Base Excision Repair Function specific endonucleases (glycosylases) remove bases that have been modified by several common mechanisms of damage e.g. deaminated cytosines (C → U) removed by uracil glycosylase can take place anytime during the cell cycle but occurs primarily in G1 Process glycosylase specific for the damaged nucleotide removed damaged base by breaking glycosidic bond damaged base removed sugar remains but base removed creates an apurinic/apyrimidinic (AP) site gap filled by DNA polymerase I this protein has 5' to 3' exonuclease activity ligation of strand nick by DNA ligase III Nucleotide Excision Repair Function removes thymidine dimers caused by UV-B light removes damaged bases caused by chemicals Process maintenance repair XPC recognises DNA lesion and recruits XPA XPB-G binds DNA and removes a chunk spanning the damaged segment DNA polymerase fills the gap DNA ligase seals the nick transcription-coupled repair RNA polymerase stalls at DNA lesion CSB and XPG recognize stalled RNA polymerase CSA joins complex and removes damaged site and allows transcription to continue Deficiency xeroderma pigmentosum (XP) cause lack any enzyme XPA - XPG presentation cannot repair UV damage sunlight sensitivity ↑↑↑ prevalence of skin cancer corneal ulcers diagnosis measurement of repair mechanisms in white blood cells treatment avoidance of sunlight Cockayne syndrome cause lack of CSA or CSB AR presentation growth failure photosensitivity nervous system abnormalities can affect any organ system Homologous Recombination Function repair double-strand breaks requires a sister chromatid to use as a template therefore must occur after S phase of cell cycle Process double-strand break recognized by MRN complex BRCA and BLM enzymes involved in end processing Holliday junctions are formed cross-shaped structures that mediate strand rejoining junctions are resolved may result in loss of heterozygosity due to the use of the opposite strand as a template Deficiency Bloom syndrome cause lack of BLM helicase enzyme presentation short stature rash from sun exposure café-au-lait spot leukemias, lymphomas, carcinomas BRCA-1 involved in breast, prostate, and ovarian cancer BRCA-2 involved in breast cancer Non-Homologous End Joining Function repair double-strand breaks these breaks may be caused by ionizing radiation or oxidative free radicals mechanism of cancer radiation therapy occurs when a sister chromatid is not available to use as a template (prior to S phase of cell cycle) Process break recognized by MRN complex additional enzymes (Artemis, XLF, Pol μ) cut ends so they can bind DNA ligase IV joins ends together Deficiency severe combined immunodeficiency disease (SCID) one of many causes
QUESTIONS 1 of 11 1 2 3 4 5 6 7 8 9 10 11 Previous Next Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.BC.15.73) A 3-year-old male child is found to have a disease involving DNA repair. Specifically, he is found to have a defect in the endonucleases involved in the nucleotide excision repair of pyrimidine dimers. Which of the following is a unique late-stage complication of this child's disease? QID: 106551 Type & Select Correct Answer 1 Colorectal cancer 12% (38/307) 2 Endometrial cancer 1% (4/307) 3 Lymphomas 6% (17/307) 4 Telangiectasia 9% (27/307) 5 Malignant melanoma 70% (216/307) M 4 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic (M1.BC.14.27) A 5-month-old male infant from a consanguineous marriage presents with severe sunburns and freckling in sun exposed areas. The mother explains that the infant experiences these sunburns every time the infant goes outside despite applying copious amounts of sunscreen. Which of the following DNA repair mechanisms is defective in this child? QID: 107023 Type & Select Correct Answer 1 Nucleotide excision repair 78% (93/119) 2 Base excision repair 10% (12/119) 3 Mismatch repair 4% (5/119) 4 Homologous recombination 3% (4/119) 5 Non-homologous end joining 0% (0/119) M 2 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 1 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.BC.13.26) A 65-year-old male is treated for anal carcinoma with therapy including external beam radiation. How does radiation affect cancer cells? QID: 100091 Type & Select Correct Answer 1 Induces the formation of thymidine dimers 21% (92/436) 2 Induces the formation of disulfide bonds 2% (7/436) 3 Induces G/T and A/C pair formation 3% (11/436) 4 Induces deamination of cytosine 4% (19/436) 5 Induces breaks in double-stranded DNA 69% (300/436) M 1 Question Complexity E Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 5 Review Tested Concept Review Full Topic Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK
All Videos (4) Login to View Community Videos Login to View Community Videos Xeroderma Pigmentosum Biochemistry - DNA Repair D 3/11/2019 537 views 4.7 (6) Login to View Community Videos Login to View Community Videos Non-homologous end joining repair system Chris Robinson Biochemistry - DNA Repair D 2/11/2015 184 views 4.3 (6) Login to View Community Videos Login to View Community Videos Homology-dependent double strand break repair Biochemistry - DNA Repair E 2/11/2015 243 views 3.2 (6) Biochemistry | DNA Repair Biochemistry - DNA Repair Listen Now 14:16 min 8/10/2021 51 plays 5.0 (1) See More See Less