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 login to view 1 more bullet error prone login to view 1 more bullet 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 login to view 4 more bullets presentation login to view 6 more bullets 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 login to view 1 more bullet presentation login to view 4 more bullets diagnosis login to view 1 more bullet treatment login to view 1 more bullet Cockayne syndrome cause login to view 1 more bullet AR presentation login to view 4 more bullets 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 login to view 1 more bullet presentation login to view 4 more bullets 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