Front Cover -- DNA Repair -- Copyright -- Contents -- Contributors -- Preface -- Chapter One: DNA repair by photolyases -- 1. Introduction -- 2. Cryptochrome/photolyase protein family -- 2.1. Cofactors of the photolyases -- 2.2. The crystal structure of the photolyase -- 2.3. Reaction mechanism of DNA repair mediated by CPD photolyase -- 2.4. Reaction mechanisms of DNA repair mediated by (6-4) and other classes of the photolyases -- 3. Conclusion -- Acknowledgment -- References -- Chapter Two: TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA repair -- 1. Introduction -- 2. Composition, topology and structure of TFIIH -- 2.1. TFIIH composition: 10 subunits and more -- 2.2. Topology and structure of TFIIH -- 3. The XPB translocase and the XPD helicase -- 3.1. XPB: A translocase rather than a helicase -- 3.2. XPD a bona fide helicase: Damage recognition and DNA opening -- 4. Regulatory core-TFIIH subunits -- 4.1. The p34/p44 pair: Regulation of XPD helicase -- 4.2. p52 and p8: Modulation of XPB activity -- 4.3. p62: An anchor for partners -- 5. Transcription regulation: The role of TFIIH -- 5.1. Promoter opening -- 5.2. Promoter escape -- 6. TFIIH in nucleotide excision repair -- 6.1. XPC-mediated detection of DNA lesions and recruitment of TFIIH -- 6.2. TFIIH opens DNA and verifies the damage -- 6.3. TFIIH-mediated enrollment of the XPG endonuclease -- 7. TFIIH, human diseases and next generation cancer therapies -- 7.1. Molecular basis of XP, CS and TTD: Insights into TFIIH regulation -- 7.2. Viral pathogenesis -- 7.3. TFIIH as a therapeutic target: Small molecule inhibitors -- 8. Conclusions -- Acknowledgments -- References -- Chapter Three: Chromatin control in double strand break repair -- 1. DNA repair and chromatin -- 2. Chromatin control of double strand break repair -- 2.1. Mechanisms of DSB repair.

3. Chromatin in the temporal control of DSB repair -- 3.1. DNA damage signaling -- 3.2. Chromatin events leading to DSB repair pathway choice -- 4. Spatial control of DSB repair -- 4.1. Control of local chromatin accessibility -- 4.2. Large scale re-organization of the repair process -- 4.3. The nucleolus as a hub involved in genome integrity maintenance -- 5. Concluding remarks -- Acknowledgments -- References -- Chapter Four: Controlling the balance between chromosome break repair pathways -- 1. Reacting to chromosome breaks -- 2. The DNA damage response -- 3. The repair of DNA double strand breaks -- 3.1. Non-homologous DNA end-joining -- 3.2. Alternative non-homologous end-joining -- 3.3. Homologous recombination -- 4. DNA end resection -- 5. Local chromatin environment controls DNA end resection and homologous recombination -- 5.1. Resection and DSB repair in euchromatin and heterochromatin -- 5.2. Chromatin remodeler complexes that participate in DSB repair -- 5.2.1. The INO80 group -- 5.2.2. The SWI/SNF group -- 5.2.3. The ISWI group -- 5.2.4. The CHD group -- 6. The connection between the metabolism of RNA and DSB repair pathway choice -- 6.1. ncRNAs and DSB repair -- 6.1.1. miRNAs -- 6.1.2. Long non-coding RNAs in DSB repair -- 6.1.3. RNA:DNA hybrids and DNA repair -- 6.2. The role of RNA-related factors in DSB repair -- 7. Concluding remarks -- References -- Chapter Five: Targeting DNA repair in precision medicine -- 1. Introduction -- 2. DNA repair pathways -- 2.1.1. Base excision repair (BER) -- 2.1.2. Nucleotide excision repair (NER) -- 2.2. Homologous recombination (HR) -- 2.3. Nonhomologous end joining (NHEJ) -- 3. DNA repair targets as therapeutic strategies -- 3.1. Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) -- 3.2. Rad51 -- 3.3. Poly ADP-ribose polymerase 1 (PARP-1) -- 3.4. PARPi and ionizing radiation (IR).

3.5. PARPi and epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) -- 3.6. PARPi and immune checkpoints -- 4. DNA repair checkpoints -- 4.1. Checkpoint kinase 1 (CHK1) and checkpoint kinase 2 (CHK2) -- 4.2. Wee1 -- 4.3. Cyclin dependent kinases 4 and 6 (CDK4/6) -- 4.4. DNA dependent protein kinase (DNA-PK) and ionizing radiation (IR) -- 5. Summary -- References -- Chapter Six: Replication stress: Driver and therapeutic target in genomically instable cancers -- 1. Introduction -- 2. DNA replication -- 2.1. Licensing and firing -- 3. Replication stress -- 3.1. MYC -- 3.2. Cyclin E -- 3.3. RAS -- 4. How to deal with RS -- 4.1. ATR-CHK1 signaling -- 4.2. Replication fork protection -- 4.3. Homologous recombination repair -- 4.4. The Fanconi anemia pathway, translesion synthesis and alternative end-joining -- 4.5. Mitotic processing of replication-born lesions -- 5. Targeting replication stress in cancer -- 5.1. Induction of replication catastrophe -- 5.2. Targeting oxidized nucleosides -- 5.3. Targeting cell cycle checkpoint kinases -- 5.4. Targeting replication stress in mitosis -- 5.5. Immune-checkpoint inhibitors -- 5.6. Biomarkers to identify tumors with replication stress -- 6. Concluding remarks -- Acknowledgments -- References -- Chapter Seven: Claspin: From replication stress and DNA damage responses to cancer therapy -- 1. Introduction -- 2. Claspin, DNA replication, and replication stress -- 2.1. Claspin and DNA replication -- 2.2. Claspin and the replication stress response -- 3. Claspin and the DNA damage response -- 3.1. Claspin and checkpoint activation in response to DNA damage -- 3.2. Claspin and DNA repair -- 4. Claspin as a target for chemo- and radio-sensitization -- 4.1. Inhibitors targeting RSR -- 4.2. Inhibitors targeting DNA repair pathways -- 4.3. A rationale for targeting Claspin.

5. Conclusions and perspectives -- References -- Chapter Eight: cAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy -- 1. Melanoma: A growing problem -- 1.1. Epidemiology -- 1.2. UV exposure -- 1.3. Indoor tanning -- 1.4. Immunodeficiency -- 1.5. Chemical exposure -- 1.6. Fair skin complexion -- 1.7. Family history of skin cancer -- 1.8. Nevi (moles) -- 2. Melanocortin 1 receptor (MC1R) -- 2.1. MC1R structure and polymorphisms -- 2.2. Melanocortin-mediated MC1R cAMP signaling -- 3. Melanins -- 3.1. Eumelanin vs. pheomelanin -- 3.2. MC1R antagonists -- 4. Role of ultraviolet light in DNA damage -- 4.1. UV mutagenesis -- 4.2. UV and melanoma link -- 5. Repair of DNA damage -- 5.1. Melanoma and DNA repair defects -- 5.2. Nucleotide excision repair (NER) -- 6. Intersection of melanocytes and NER -- 6.1. MC1R-cAMP signaling and NER -- 6.2. Influence of MC1R ligands on NER -- 6.3. Relevance of MC1R signaling pathway beyond UV -- 6.4. Additional mechanisms of regulating melanocyte NER -- 6.5. Translational implications: Enhancement of melanocyte genomic stability for melanoma prevention -- Acknowledgments -- Conflicts of interest -- References -- Chapter Nine: Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling -- 1. Introduction -- 2. DNA metabolic factors negatively regulate immune signaling -- 2.1. Role of NBS1 in innate immune signaling -- 2.2. Role of ATM in innate immune signaling -- 2.3. Role of RAD51 in innate immune signaling -- 2.4. Role of BRCA1 in immune signaling -- 2.5. Role of Fanconi anemia pathway factors in immune signaling -- 2.6. Role of DNA-PK in immune signaling -- 2.7. Role of meiotic recombination 11 homolog A (MRE11) in immune signaling -- 2.8. Role of MMS and UV-sensitive protein 81 (MUS81) in immune signaling.

2.9. Role of three prime repair exonuclease 1 (TREX1) in immune signaling -- 3. Mechanisms of immune signaling regulation by DDR factors -- 3.1. Generation of chromatin fragments due to defective G2/M checkpoint -- 3.2. Degradation of replication forks by nucleases -- 3.3. Failure to retain fragmented self-DNA within the nucleus -- 3.4. Direct sensing of DNA in the cytoplasm -- 3.5. Removal of self-DNA from the cytoplasm -- 4. Consequences of defective DDR factors mediated immune signaling -- 4.1. Cytosolic DNA sensing pathway-mediated cellular senescence -- 4.2. Crosstalk among defective DDR factors, immune signaling and cancer -- 4.3. Interconnection between defective DDR factors and autoinflammatory disease -- 5. Conclusions -- Acknowledgments -- References -- Chapter Ten: Elucidating the role of interacting residues of the MSH2-MSH6 complex in DNA repair mechanism: A computation ... -- 1. Introduction -- 2. Materials and methods -- 2.1. Dataset -- 2.2. Pathogenicity analysis -- 2.3. Stability analysis -- 2.4. Conservation analysis -- 2.5. Molecular dynamics simulations (MDS) -- 3. Results -- 3.1. Protein-protein interaction -- 3.2. Pathogenicity analysis -- 3.3. Stability analysis -- 3.4. Conservation analysis -- 3.5. Molecular dynamics simulations -- 4. Discussion -- 5. Conclusion -- Acknowledgments -- Disclosure statement -- References -- Further reading -- Chapter Eleven: A computational model to predict the structural and functional consequences of missense mutations in O-me ... -- 1. Introduction -- 2. Materials and methods -- 2.1. Experimental design -- 2.2. Dataset -- 2.3. Pathogenicity and stability of the mutants -- 2.4. Conservation analysis -- 2.5. Mutant modeling and molecular dynamics -- 3. Results -- 3.1. Data set -- 3.2. Pathogenicity analysis -- 3.3. Stability analysis -- 3.4. Conservation analysis -- 3.5. Molecular dynamics.

4. Discussion.