PALB2 (partner and Localizer of BRCA2) binds to the N-terminal region of BRCA2, and is vital for its function by facilitating its subnuclear localization []. It binds BRCA1 and BRCA2 and serves as the molecular scaffold in the formation of the BRCA1-PALB2-BRCA2 complex, which is required for homologous recombination repair []. It has also been shown to bind DNA and physically interacts with RAD51 []. Biallelic mutations in PALB2 cause Fanconi anemia (FA) subtype FA-N, whereas monoallelic mutations predispose to breast, and pancreatic familial cancers[].
RAD51-associated protein 1 may participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair []. It functionally cooperates with PALB2 in promoting of D-loop formation by RAD51 [, ]. It binds to single and double stranded DNA, and is capable of aggregating DNA []. It also binds RNA []. It is phosphorylated upon DNA damage, probably by ATM or ATR [, , ].
Mortality factor 4-like protein 1 (MORF4L1 or MRG15) is a transcription factor and a chromodomain protein. It is a component of the NuA4 histone acetyltransferase complex [], the Sin3 complex which acts to repress transcription by deacetylation of nucleosomal histones [], and the nuclear protein complexes MAF1 and MAF2 []. MRG15 also interacts with the BRCA complex, especially with subunit PALB2 []. MRG15 has an MRG domain in its C-terminal region, which interacts with the nucleoprotein PAM14 during transcriptional regulation [].The NuA4 histone acetyltransferase complex (also known as the TRRAP/TIP60-containing histone acetyltransferase complex) acetylates nucleosomal histones H4 and H2A thereby activating selected genes for transcription and is a a key regulator of transcription, cellular response to DNA damage and cell cycle control []. In yeast, where the complex was first identified, NuA4 consists of at least ACT1, ARP4, YAF9, VID21, SWC4, EAF3, EAF5, EAF6, EAF7, EPL1, ESA1, TRA1 and YNG2 []. In humans, the complex is composed of the histone acetyltransferase KAT5 (also known as TIP60) plus the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, MAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6 [].
This entry represents XPG (ERCC-5, alsoknown as Rad2 in budding yeast, AtRAD2 or UVH3 in Arabidopsis and Rad13 in fission yeast), a single-stranded structure-specific DNA endonuclease, which cleaves single-stranded DNA during nucleotide excision repair to excise damaged DNA []. It makes the 3' incision in DNA nucleotide excision repair (NER); it binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble [, ]. XPG is required for DNA replication fork maintenance and preservation of genomic stability [, ]. It is involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site []. During HRR, binds to the replication fork with high specificity and stabilizes it []and upstream of HRR, it promotes the release of BRCA1 from DNA [].In Saccharomyces cerevisiae, Rad2 forms the Nucleotide Excision Repair Factor 3 (NEF3) complex with a subset of subunits of the transcription factor TFIIH []. Besides DNA damage repair, it is also required for efficient transcription []. Defects in XPG are the cause of xeroderma pigmentosum complementation group G (XP-G), which is an autosomal recessive pigmentary skin disorder characterised by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities [].
