Ne tiedot voat 2004 ajalta. Nyt luin siitä että fytiini on mukana NHEJ:ssä Joten otan nämä asiat esiin.
Löydän tämän: http://www.sciencedirect.com/science/article/pii/S1568786415000737
Cell cycle regulation of human DNA repair and chromatin remodeling genes
- Under a Creative Commons license
3.10. Genes encoding proteins for non-homologous end joining (NHEJ) – a regulatory role for PTTG/securin
Generally, genes centrally involved in NHEJ were found not to be cell cycle regulated (Fig. 8). However, PTTG1,
encoding the 202 amino acids protein PTTG1 (also called securin),
consistently had the highest transcript level at the M/G1-transition in
all data sets and then declines rapidly during the G1 phase. PTTG1 is a
multifunctional and rather intriguing protein. It binds directly to Ku70
(also called XRCC6) and functions as a negative regulator of NHEJ [73] and [74].
Thus, PTTG1 may inhibit illegitimate NHEJ until completion of
replication.
It was reported that PTTG1 is ubiquitinated at metaphase-anaphase transition by the E3 ligase anaphase-promoting complex (APC). It is then normally rapidly degraded in proteasomes (reviewed in [75]), thus alleviating the NHEJ-inhibition and reestablishing the capacity for NHEJ during G1 phase.
Importantly, PTTG1 also controls sister chromatid separation during mitosis by binding to and inhibiting separase, which when active cleaves cohesin that holds sister chromatids together [76]. Normal levels of PTTG1 may prevent premature sister chromatid separation, thus facilitating DNA repair by HRR during the S phase and G2.
However, overexpression of PTTG1 correlates strongly with aneuploidy in breast cancer [77], possibly due to an inability of sister chromatids to separate. Overexpression of PTTG1 is associated with a wide range of malignancies, e.g. hematopoietic malignancies [78], colon cancer [79] and breast cancer [80].
Thus, while PTTG1 normally regulates several processes important to genomic stability, overexpression appears to promote genomic instability, stimulate proliferation and contribute to carcinogenesis. PTTG1 also functions as a transcriptional regulator of several genes involved in tumorigenesis [81].
We conclude that normally the transcript level of PTTG1 is upregulated at the M/G1-transition, but subsequently ubiquitinylated and degraded in proteasomes at metaphase-anaphase transition, allowing chromatid separation.
Overexpression of PTTG1 apparently results in inability of sister chromatids to separate with increased risk of aneuploidy in cancer cells [82] and [83].
It was reported that PTTG1 is ubiquitinated at metaphase-anaphase transition by the E3 ligase anaphase-promoting complex (APC). It is then normally rapidly degraded in proteasomes (reviewed in [75]), thus alleviating the NHEJ-inhibition and reestablishing the capacity for NHEJ during G1 phase.
Importantly, PTTG1 also controls sister chromatid separation during mitosis by binding to and inhibiting separase, which when active cleaves cohesin that holds sister chromatids together [76]. Normal levels of PTTG1 may prevent premature sister chromatid separation, thus facilitating DNA repair by HRR during the S phase and G2.
However, overexpression of PTTG1 correlates strongly with aneuploidy in breast cancer [77], possibly due to an inability of sister chromatids to separate. Overexpression of PTTG1 is associated with a wide range of malignancies, e.g. hematopoietic malignancies [78], colon cancer [79] and breast cancer [80].
Thus, while PTTG1 normally regulates several processes important to genomic stability, overexpression appears to promote genomic instability, stimulate proliferation and contribute to carcinogenesis. PTTG1 also functions as a transcriptional regulator of several genes involved in tumorigenesis [81].
We conclude that normally the transcript level of PTTG1 is upregulated at the M/G1-transition, but subsequently ubiquitinylated and degraded in proteasomes at metaphase-anaphase transition, allowing chromatid separation.
Overexpression of PTTG1 apparently results in inability of sister chromatids to separate with increased risk of aneuploidy in cancer cells [82] and [83].
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