Our interest in understanding the complex interrelationships between DNA repair, cancer and senescence has led us to study the role of DNA repair in several human model systems which are pertinent to both cancer and aging. We and others have identified specific DNA repair phenotypes characteristic of a group of related heritable cancer prone and progeroid human syndromes that have heterogenous clinical manifestations. The role of human DNA repair phenotypes in mutation induction, distribution, and in tumor formation has been explored. By studying gene-specific DNA repair and specifically repair of the p53 tumor suppressor gene in cancer prone disorders, we have been able to further characterize the correlations between DNA repair, mutation distribution, and cancer risk. By investigating DNA damage induction and repair in progeroid syndromes such as Werner's syndrome, we can examine a human mutant which has several clinical manifestations concordant with normal human aging and also associated with an increased cancer incidence. Alzheimer's disease also provides a useful model system in which to study the role of DNA repair in a condition associated with senescence. We have measured gene-specific repair in fibroblasts from patients with familial and sporadically occurring Alzheimer's disease. Telomeric shortening is one of the age-associated genetic instabilities currently believed to be an important biomarker of aging and cancer. We have developed a novel method to measure DNA damage induction and repair in human telomeres and suspect that repair capacity in telomeres may be related to the genomic instability associated with normal human aging and perhaps with tumorigenesis.
| Ramamoorthy, Mahesh; May, Alfred; Tadokoro, Takashi et al. (2013) The RecQ helicase RECQL5 participates in psoralen-induced interstrand cross-link repair. Carcinogenesis 34:2218-30 |
| Popuri, Venkateswarlu; Tadokoro, Takashi; Croteau, Deborah L et al. (2013) Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability. Crit Rev Biochem Mol Biol 48:289-99 |
| Ferrarelli, Leslie K; Popuri, Venkateswarlu; Ghosh, Avik K et al. (2013) The RECQL4 protein, deficient in Rothmund-Thomson syndrome is active on telomeric D-loops containing DNA metabolism blocking lesions. DNA Repair (Amst) 12:518-28 |
| Croteau, Deborah L; Rossi, Marie L; Ross, Jennifer et al. (2012) RAPADILINO RECQL4 mutant protein lacks helicase and ATPase activity. Biochim Biophys Acta 1822:1727-34 |
| Popuri, Venkateswarlu; Ramamoorthy, Mahesh; Tadokoro, Takashi et al. (2012) Recruitment and retention dynamics of RECQL5 at DNA double strand break sites. DNA Repair (Amst) 11:624-35 |
| Singh, Dharmendra Kumar; Popuri, Venkateswarlu; Kulikowicz, Tomasz et al. (2012) The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability. Nucleic Acids Res 40:6632-48 |
| Kanagaraj, Radhakrishnan; Parasuraman, Prasanna; Mihaljevic, Boris et al. (2012) Involvement of Werner syndrome protein in MUTYH-mediated repair of oxidative DNA damage. Nucleic Acids Res 40:8449-59 |
| Ramamoorthy, Mahesh; Tadokoro, Takashi; Rybanska, Ivana et al. (2012) RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression. Nucleic Acids Res 40:1621-35 |
| Speina, Elzbieta; Dawut, Lale; Hedayati, Mohammad et al. (2010) Human RECQL5beta stimulates flap endonuclease 1. Nucleic Acids Res 38:2904-16 |
| Schurman, Shepherd H; Hedayati, Mohammad; Wang, ZhengMing et al. (2009) Direct and indirect roles of RECQL4 in modulating base excision repair capacity. Hum Mol Genet 18:3470-83 |
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