We are studying the role of DNA repair processes in cancer and senescence. The goal is to determine whether there are detectable deficiencies in DNA repair in these two related conditions. Gene specific DNA repair has been measured in cells from patients with cancer prone and premature aging syndromes. Whereas we can not detect changes or deficiencies in the cancer prone syndromes, there is a lack of preferential DNA repair of active genes in at least one premature aging syndrome, Cockayne syndrome. In the human syndrome, Fanconi's anemia, we find that there is a deficiency in DNA repair, for both DNA lesions introduced by cisplatin. We have investigated the role of DNA repair in drug resistance. In cisplatin resistant human ovarian cancer cell lines we found a gene specific DNA repair alteration: an increase in the DNA repair efficiency of cisplatin interstrand crosslinks. This may be an important element in the resistant phenotype. Telomeric length is one of the best available biomarkers of aging. A shortening of telomeric length with aging has been observed in many biological systems. We are measuring DNA damage and repair in these critical end-regions of the chromosomes that are also very important for genomic stability.
| 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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