The DNA resection protein CtIP promotes mammary tumorigenesis

摘要: Many DNA repair factors act to suppress tumor formation by preserving genomic stability. Similarly, the CtIP protein, which interacts with BRCA1 suppressor, is also thought have suppression activity. Through its role in end resection, facilitates double-strand break (DSB) homologous recombination (DSBR-HR) and microhomology-mediated joining (MMEJ). In addition, however, has been implicated of aberrant chromosomal rearrangements an MMEJ-dependent manner, activity that could potentially promote development increasing genome instability. To clarify whether acts vivo or tumorigenesis, we examined oncogenic potential mouse models human breast cancer. Surprisingly, mice heterozygous for a null Ctip allele did not display increased susceptibility formation. Moreover, mammary-specific biallelic ablation elicit tumors manner reminiscent loss. Instead, inactivation dramatically reduced kinetics mammary tumorigenesis bearing lesions p53 gene. Thus, unlike other factors, but properties can consistent ability facilitate Consequently, inhibition CtIP-mediated MMEJ may prove effective against types, such as cancer, rearrangements.